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  • 101
    Digitale Medien
    Digitale Medien
    The intra- and inter-subject variability of Nifedipine pharmacokinetics in young volunteers (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 57-60 
    Details
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; pharmacokinetics ; oral contraceptives ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations of Nifedipine were measured following single oral doses of Nifedipine Slow Release (Adalat Retard) on three separate occasions to young, healthy volunteers of both sexes. Intra- and inter-subject variability were assessed by comparing the pharmacokinetic parameters, AUC, Cmax and T50%AUC. Interindividual variability was less than that observed in other studies with the betablockers, metoprolol and propranolol and there was no evidence of differences between the sexes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614196
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  • 102
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and pharmacodynamics of the prostacyclin analogue iloprost in man (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 61-68 
    Details
    ISSN: 1432-1041
    Schlagwort(e): iloprost ; prostacyclin analogue ; pharmacokinetics ; platelet aggregation ; healthy male volunteers ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma levels of the prostacyclin analogue, iloprost, were measured by antibody/GC/MS in healthy male volunteers given 1 and 3 ng/kg per min i.v. for 45 min, and 1 µg/kg p.o. Following i.v. infusion, the steady-state plasma levels of iloprost were strictly dose-dependent (46±8 pg/ml and 135±24 pg/ml). The disposition was biphasic with half-lives of 3–4 min and 0.5 h. After oral administration, absorption of the drug was extremely rapid, the maximum plasma level of 251±32 pg/ml being achieved after 10±6 min. The bioavailability was 16±4%. Platelet aggregation induced by 2 µM ADP was reduced by 53% and 68% at the end of the two different infusions, and by 68% 15 min after p.o. administration. The ex-vivo inhibition of platelet aggregation by iloprost was not affected by preceding drug treatment. The cAMP content of platelets was increased by a factor of 2.5 at the end of the infusions and to a lesser extent 15 min after oral dosing. A slight increase in heart rate occurred during the infusion and within 30 min after oral administration; blood pressure was virtually unaffected. Except for transient side-effects (facial flush and headache) no adverse reactions were observed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614197
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  • 103
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of methysergide and its metabolite methylergometrine in man (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 75-77 
    Details
    ISSN: 1432-1041
    Schlagwort(e): methysergide ; methylergometrine ; first-pass metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five healthy men were given 1.0 mg methysergide maleate intravenously and 2.7 mg methysergide maleate orally in a cross-over study. The systemic availability of methysergide was only 13%, most probably due to a high degree of first-pass metabolism to methylergometrine. We also found evidence of extrahepatic clearance of methysergide. After oral administration the plasma concentrations of the metabolite were considerably higher than those of the parent drug and the area under the plasma concentration curve (AUC) for methylergometrine was more than ten times greater than for methysergide. Our findings may be relevant to the treatment of migraine if methylergometrine contributes to the effect of methysergide. Methylergometrine had a significantly longer elimination half-life than methysergide (223±43 min vs 62.0±8.3 min and 174±35 min vs 44.8±8.1 min in the oral and intravenous studies respectively).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614199
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  • 104
    Digitale Medien
    Digitale Medien
    Effect of cirrhosis and renal failure on the kinetics of clotiazepam (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 89-92 
    Details
    ISSN: 1432-1041
    Schlagwort(e): clotiazepam ; liver cirrhosis ; renal insufficiency ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of a single 5-mg oral dose of the thienodiazepine clotiazepam was evaluated in a series of patients with biopsy-proven cirrhosis, and in patients with renal insufficiency requiring maintenance hemodialysis, compared to healthy matched controls. Clotiazepam volume of distribution (Vz) was significantly smaller in cirrhotic patients than in controls (1.83 vs 2.57 l/kg), and total clearance was likewise reduced (2.15 vs 3.15 ml/min/kg). Elimination half-life was similar between groups (10.0 vs. 10.2h). There were no significant differences between renal failure and control patients in clotiazepam Vz, oral clearance, or elimination half-life. Thus cirrhosis is associated with reduced clearance of clotiazepam, probably due to impairment of its microsomal oxidation. However clotiazepam disposition is not significantly altered in dialysis-dependent renal insufficiency patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614202
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  • 105
    Digitale Medien
    Digitale Medien
    The effects of age and chronic liver disease on the elimination of temazepam (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 93-97 
    Details
    ISSN: 1432-1041
    Schlagwort(e): temazepam ; liver disease ; elimination ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of the newer 1, 4 benzodiazepine temazepam were evaluated in 16 healthy subjects aged 18–92 years and in 15 cirrhotic patients, to ascertain the effect of ageing and liver disease. The data were analysed both by classic two compartment and by non-compartmental methods. The mean elimination half-life in the control subjects was 15.5 h, considerably longer than previous estimates. No correlation was found between age and pharmacokinetic parameters. The cirrhotic group showed no statistically significant difference in the pharmacokinetic parameters nor in the urinary recovery of the dose from the control group. Temazepam plasma protein binding was assessed in a second group of 9 cirrhotics of similar severity to the main group and in matched controls. When these binding data were applied to the mean clearance data, a modest although not statistically significant, reduction in free drug clearance was observed in the cirrhotic group. This study adds further support to the observation that drugs which undergo ether glucuronidation have normal elimination patterns in patients with liver disease. Temazepam may prove to be a useful hypnotic sedative in patients with liver disease.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614203
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  • 106
    Digitale Medien
    Digitale Medien
    Cirrhosis of the liver markedly impairs the elimination of mexiletine (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 83-88 
    Details
    ISSN: 1432-1041
    Schlagwort(e): mexiletine ; cirrhosis of the liver ; antiarrhythmic agents ; pharmacokinetics ; intravenous administration ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To study the effects of cirrhosis of the liver on the pharmacokinetics of mexiletine a single i.v. dose of 200 mg was administered to six cirrhotic patients and to six healthy controls. The distribution of mexiletine in both study groups was similar, as indicated by similar values of V1 and Vss, but it tended to occur more slowly in the cirrhotics. The plasma protein binding of mexiletine was unchanged in the patients with cirrhosis. The elimination of mexiletine was markedly retarded in the cirrhotics, as indicated by its lower total clearance (2.31 vs. 8.27 ml/kg/h,) lower total elimination rate constant (0.059 vs 0.353 h−1), and longer elimination half-life (28.7 vs 9.9 h). The antipyrine half-life was 38.3 h in the patients and 14.7 h in the controls. One healthy volunteer had a Morgagni-Stokes-Adams type of syncopal attack 5 min after administration of mexiletine due to disturbance of AV conduction induced by the drug. Thus, on a pharmacokinetic basis the loading dose of mexiletine need not be modified in cirrhotic patients, whereas the maintenance dosage should be reduced to one fourth — one third of the usual dose.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614201
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  • 107
    Digitale Medien
    Digitale Medien
    Ceftriaxone pharmacokinetics following multiple intramuscular dosing (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 109-112 
    Details
    ISSN: 1432-1041
    Schlagwort(e): ceftriaxone ; intramuscular ; pharmacokinetics ; steady-state
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The steady-state pharmacokinetics and tolerance of ceftriaxone after multiple i.m. doses of 0.5 and 1 g q12 h for 3.5 days were investigated in 12 healthy, adult volunteers. Ceftriaxone was rapidly absorbed after i.m. administration with mean peak times ranging from 1.3 to 1.9 h. Steady-state plasma concentrations were apparent after the third dose of both dosage regimens, with trough plasma concentrations of 24±6 and 39±8 µg/ml (mean±SD) after the 0.5 and 1 g q12 h regimens, respectively. Multiple i.m. administrations of ceftriaxone did not alter its elimination half-life; however, small increases were observed in the plasma clearance and volume of distribution at the 1-g regimen. These increases were attributed to the non-linear binding of ceftriaxone to human plasma proteins, and are therapeutically unimportant. Ceftriaxone was well tolerated and serious or lasting adverse reactions were not encountered in the study.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614206
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  • 108
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of dezocine, a new analgesic: Effect of dose and route of administration (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 121-123 
    Details
    ISSN: 1432-1041
    Schlagwort(e): dezocine ; opioid analgesics ; pharmacokinetics ; healthy volunteers ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of intravenous (IV) dezocine, and bioavailability of intramuscular (IM) and subcutaneous (SQ) dezocine, were evaluated in healthy male volunteers. Elimination half-life following 5, 10, and 20 mg IV doses averaged 2.6–2.8 h, and was independent of dose. Clearance decreased slightly, although significantly, with dose. After Deltoid IM injection, dezocine was rapidly absorbed (peak level: 0.6 h after dose), with bioavailability 97%. Thus dezocine has extensive distribution, high clearance and short half-life over a range of IV doses. It is rapidly and completely absorbed following IM or SQ administration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614208
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  • 109
    Digitale Medien
    Digitale Medien
    Comparison of single and multiple dose pharmacokinetics of theophylline using stable isotopes (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 113-120 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; pharmacokinetics ; stable isotopes ; diurnal variation ; single dose administration ; multiple dose administration ; systemic availability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Theophylline, enriched with the stable isotopes13C and15N, was administered intravenously in a dose of 10 mg to 8 healthy men following single (200 mg) and multiple (200 mg 8-hourly for 5 days) oral dose administration of aminophylline. Total plasma clearance, volume of distribution, and half-time determined from the intravenous data were similar, demonstrating that the pharmacokinetics of theophylline after chronic dosing can be predicted from the pharmacokinetics of a single dose. With chronic oral dosing, however, the mean trough concentration was 12% higher at 9 a.m. than at 5 p.m., the end of the dose interval (3.94±0.55 vs. 3.50±0.45 µg·ml−1). The AUC following oral dosing was 25% higher in the multiple dose study than in the single dose study. Simulation analysis suggested that these results could be explained by diurnal variation in the clearance or absorption rate or a combination of both. Thus, the systemic availability of theophylline measured during a single dosage interval after chronic oral dosing to steady state would be overestimated in comparison with that measured after a single oral dose.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614207
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  • 110
    Digitale Medien
    Digitale Medien
    Single dose oxazepam has no effect on acetaminophen clearance or metabolism (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 127-129 
    Details
    ISSN: 1432-1041
    Schlagwort(e): oxazepam ; acetaminophen clearance ; metabolite formation ; glucuronidation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The metabolism of acetaminophen and oxazepam in humans is mainly dependent on the microsomal capacity for glucuronide conjugation. The clearance of acetaminophen and the formation of metabolites were evaluated in 7 patients before and during concomitant administration of oxazepam 30 mg. The subjects received a single 500 mg dose of acetaminophen i.v. and concentrations in plasma were measured for 360 minutes and in urine for 24 h in order to estimate the production of metabolites. The single therapeutic dose of oxazepam had no effect on the clearance of acetaminophen or on formation of its metabolites.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614210
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  • 111
    Digitale Medien
    Digitale Medien
    Treatment of essential hypertension with felodipine in combination with a diuretic (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 133-139 
    Details
    ISSN: 1432-1041
    Schlagwort(e): felodipine ; hydrochlorothiazide ; essential hypertension ; calcium antagonist ; pharmacokinetics ; plasma noradrenaline ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a double-blind cross-over study, the effect on blood pressure (BP), heart rate (HR) and plasma noradrenaline concentration (pNA) of placebo or felodipine given in addition to hydrochlorothiazide was studied in 12 male patients with essential hypertension, not satisfactorily controlled with the diuretic alone. The first dose of felodipine decreased BP and increased HR for about 6 h. After 4 weeks of treatment with felodipine, BP was reduced for 24 h, whereas HR was only transiently increased. The elimination half-life of felodipine was about 23 h. The plasma noradrenaline concentration increased after felodipine and serum uric acid decreased. Side-effects were few and usually mild.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614290
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  • 112
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and pharmacodynamics in man of the dopamine antagonist ergot derivative, bromerguride (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 165-168 
    Details
    ISSN: 1432-1041
    Schlagwort(e): bromerguride ; dopamine antagonist ; pharmacokinetics ; pharmacodynamics ; prolactin level ; side-effects ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma levels and urinary excretion of the dopamine antagonist, bromerguride, were measured by radioimmunoassay in healthy male volunteers given 50 µg i.v. and oral doses of 1 and 2 mg. Plasma prolactin was also measured by radioimmunoassay. Following i.v. injection, the concentration of bromerguride declined biphasically, with half-lives of 7 min and 1.2h. The total clearance was 32 ml·min−1·kg−1 and the apparent volume of distribution was 3.6 l/kg. The bioavailability of oral bromerguride was 29% after 1 mg and 25% after 2 mg. The drug was almost totally metabolized and less than 0.05% of the dose was excreted in urine in 24 h after oral administration. Plasma prolactin levels were increased in a dose-dependent manner for about 8 h. Side-effects were minimal, mainly being tiredness and headache in some of the volunteers.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606653
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  • 113
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of tenoxicam in patients with impaired renal function (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 697-701 
    Details
    ISSN: 1432-1041
    Schlagwort(e): tenoxicam ; renal insufficiency ; non-steroidal antiinflammatory agents ; protein binding ; metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of tenoxicam after a single oral dose of 20 mg has been studied in 12 patients with various degrees of decreased renal function. Unchanged tenoxicam and its 5′OH-metabolite in plasma and urine were determined by HPLC. The mean areas under the plasma concentration-time curve (138±53 µg/ml·h) and terminal half-lives in patients with impaired renal function did not differ from values previously reported in normal volunteers, nor did the peak concentration of tenoxicam. The half-life of 5′OH-tenoxicam and unchanged tenoxicam where the same. The urinary excretion of 5′OH-tenoxicam fell with decreasing renal function. Thus no dosage adjustment should be necessary and the usual daily dose of tenoxicam may be administered once daily also to patients with renal failure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00615961
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  • 114
    Digitale Medien
    Digitale Medien
    The pharmacokinetics after intravenous and oral administration in man of theα 2-adrenoreceptor antagonist idazoxan (RX781094) (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 743-745 
    Details
    ISSN: 1432-1041
    Schlagwort(e): idazoxan ; pharmacokinetics ; alpha 2-adrenoceptor antagonist ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A high performance liquid chromatographic method was developed for the quantitative determination of idazoxan in plasma. The assay was used to study the disposition of the drug after intravenous infusion and oral administration to five normal subjects. After i.v. administration the kinetics could be described by a two compartment model with a mean elimination half life of 4.20 h. The mean calculated volume of distribution during the elimination phase was 3.20 l/kg−1 and the mean plasma clearance was 824 ml min−1. After oral administration a lag period before onset of absorption was observed in all five volunteers, the plasma levels declining monoexponentially from the peak concentration with a mean elimination half life of 5.58 h. The absolute availability varied between 26% and 41% with a mean value of 34%. Invitro measurements produced a blood/plasma ratio of 1.3 for idazoxan.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00615972
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  • 115
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of temazepam in geriatric patients (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 745-747 
    Details
    ISSN: 1432-1041
    Schlagwort(e): temazepam ; pharmacokinetics ; geriatric patients ; benzodiazepines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A single dose of temazepam 10 mg, as a solution in soft gelatin capsules, was given to 10 fasting geriatric in-patients (mean age 83 years) in a stable clinical condition. The mean peak plasma concentration was 306 ng/ml, with a median time of 0.75 h to peak concentration. Temazepam was eliminated from plasma in a biexponential manner, with a distribution phase (mean t1/2α=0.7 h) predominating for 3 h. The drug had a mean elimination half-life of 8.7 h. In a chronic study, in which temazepam 10 mg p.o. was given nightly to 13 patients, the plasma concentrations on Days 3, 5, 8, 12 and 15 were not significantly different from each other, showing rapid attainment of steady state levels and the lack of drug accumulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00608229
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  • 116
    Digitale Medien
    Digitale Medien
    5-Aminosalicylic acid in patients with an ileo-rectal anastomosis (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 23-26 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sulphasalazine ; Pentasa ; slow release preparation ; 5-aminosalicylic acid ; ileo-rectal anastomosis ; ulcerative colitis ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of 5-aminosalicylic acid (5-ASA) from sulphasalazine (SASP) and the slow-release 5-ASA preparation Pentasa was investigated in a cross-over study in 9 otherwise healthy patients with an ileo-rectal anastomosis. The 24-hour recoveries of the drugs were 90.5% and 84.7%, respectively. The median release of 5-ASA from SASP was 50% and from Pentasa 75%. Equal amounts of 5-ASA (18.0% vs 17.9%) were found in the faeces, and a significantly larger amount (4.4% vs 28.9%) of the metaboliteN-acetyl-5-aminosalicylic acid (ac-5-ASA) was found in faeces following Pentasa. A larger amount of 5-ASA was absorbed and subsequently excreted in the urine, mainly as the metabolite (2.5% vs 20.5%) from Pentasa. This confirms previous results in ileostomized patients treated with Pentasa. The present findings also demonstrate that bacterial azo-reduction of SASP in patients with ileorectal anastomosis may be an adequate way to deliver 5-ASA in this type of patient. Both treatments may be used in these patients during a flare up of ulcerative colitis, but randomized studies are needed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00870980
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  • 117
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and metabolism of quinidine in extensive and poor metabolisers of sparteine (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 69-72 
    Details
    ISSN: 1432-1041
    Schlagwort(e): quinidine ; sparteine ; pharmacokinetics ; drug oxidation ; polymorphism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and metabolism of quinidine were investigated in extensive and poor metabolisers of sparteine. No differences in plasma clearance, terminal half life, volume of distribution or cumulative urinary excretion of quinidine, 3-hydroxyquinidine and quinidine-N-oxide were observed between phenotypes. Thus, it is unlikely that quinidine metabolism is controlled by the sparteine/debrisoquine gene locus.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00870989
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  • 118
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of intravenous and intraperitoneal ceftriaxone in chronic ambulatory peritoneal dialysis (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 479-483 
    Details
    ISSN: 1432-1041
    Schlagwort(e): ceftriaxone ; dialysis ; continous ambulatory peritoneal dialysis ; pharmacokinetics ; intraperitoneal administration ; intravenous administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of ceftriaxone was investigated in 8 patients without infection, who were receiving continuous ambulatory peritoneal dialysis (CAPD). Ceftriaxone 1 g was injected i.v. and 1 g was given intraperitoneally in the CAPD fluid during a 4-h dwell time. Ceftriaxone was assayed by HPLC. After intravenous administration, the kinetic parameters of ceftriaxone were: plasma t1/2, 12.3 h, total plasma clearance, 14.0 ml/min, volume of distribution at steady state 0.18 l/kg, and peritoneal clearance 0.59 ml/min. Over 72 hours only 5.5% of the dose was eliminated by the peritoneal route. After intraperitoneal administration, ceftriaxone rapidly appeared in serum; the absorption t1/2 was 1.1 h and the mean peak concentration was 38.8 µg/ml. The absorption of ceftriaxone from the peritoneal space was 39%. A single 1.0 g IP dose led to serum and dialysate concentrations of ceftriaxone above the minimum inhibitory concentration for susceptible pathogens for 24 hours.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613528
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  • 119
    Digitale Medien
    Digitale Medien
    Diuretic activity, safety and pharmacokinetics of torasemide during chronic treatment in normal subjects (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 1-7 
    Details
    ISSN: 1432-1041
    Schlagwort(e): torasemide ; diuretic activity ; pharmacokinetics ; healthy subjects ; side-effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Torasemide 40 mg/day p.o. was administered for 21 days to 8 healthy volunteers to investigate its pharmacodynamics, pharmacokinetics and safety on chronic administration. It induced a highly significant initial increase in 24-h urinary volume and 24-h excretion of sodium and chloride, but its affect diminished after the first days. On Days 0, 1, 10 and 21 the experiement was divided in 3 clearance phases, extending from 0 to 2 h, 2 to 6 h and 6 to 24 h after dosing. The fractional excretion of sodium, chloride, potassium, calcium, magnesium and inorganic phosphates peaked during the first 2 h and returned almost to the control value during the following two clearance phases. The phase-dependent changes were significant for all electrolytes, except for potassium and inorganic phosphate. Plasma electrolyte levels remained constant throughout the study, except for a small decrease in chloride and potassium and for an increase in calcium and magnesium. Fasting blood glucose and glucose tolerance test were unaffected. A small but significant decrease in LDL-cholesterol was observed on Day 10. Other plasma lipid components showed minor changes. Plasma uric acid levels were moderately increased. There was no significant change of the creatinine clearance. Body weight fell significantly (by about 2 kg) during the study. Tonal audiometry was normal before and after the study. There was no significant difference between the plasma levels of torasemide on Days 1, 10 and 21, nor between its elimination half-life on Days 1 and 21. Side-effects consisted mainly of fatigue and low-back pain on days of intense diuresis. There were no toxic symptoms. ECG recordings and blood pressure remained within normal limits.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00541460
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  • 120
    Digitale Medien
    Digitale Medien
    Comparative analysis of the pharmacokinetics of unsubstituted N1-derivatives of 1,4-benzodiazepine (1986)
    Springer
    Bulletin of experimental biology and medicine 101 (1986), S. 206-209 
    Details
    ISSN: 1573-8221
    Schlagwort(e): 1,4-benzodiazepines ; pharmacokinetics ; plasma/brain concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00836121
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  • 121
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of a water-soluble antioxidant of 3-hydroxypyridine type (1986)
    Springer
    Bulletin of experimental biology and medicine 101 (1986), S. 333-335 
    Details
    ISSN: 1573-8221
    Schlagwort(e): antioxidant ; 3-hydroxypyridines ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00835938
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  • 122
    Digitale Medien
    Digitale Medien
    Radioimmune and radioreceptor study of the pharmacokinetics of the enkephalin analog dalargin in man (1986)
    Springer
    Bulletin of experimental biology and medicine 101 (1986), S. 783-785 
    Details
    ISSN: 1573-8221
    Schlagwort(e): dalargin ; pharmacokinetics ; enkephalins
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00839605
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  • 123
    Digitale Medien
    Digitale Medien
    A dispersion model of hepatic elimination: 2. Steady-state considerations-influence of hepatic blood flow, binding within blood, and hepatocellular enzyme activity (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 261-288 
    Details
    ISSN: 1573-8744
    Schlagwort(e): hepatic elimination ; hepatic clearance ; availability ; intrinsic clearance ; pharmacokinetics ; dispersion model ; well-stirred model ; tube model ; distributed model ; blood flow ; binding within blood ; hepatocellular enzyme activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The dispersion model of hepatic elimination is based on the distribution of residence times of blood elements within the liver. The model has two asymptotic solutions corresponding to the “wellstirred” model (complete mixing of blood elements) and the “parallel-tube” model (no variation in residence times of blood elements). The steady-state form of the dispersion model relevant to pharmacokinetic analysis is developed and explored with respect to changes in blood flow, in binding within blood, and in hepatocellular enzyme activity. Literature data are used to evaluate discrepancies among the predictions of the dispersion, well-stirred, and tube models. It is concluded that the dispersion model is consistent-with the data. The limitations of steady-state perfusion experiments to estimate the residence time distribution of blood elements within the liver are considered.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01106707
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  • 124
    Digitale Medien
    Digitale Medien
    In vivo interaction of the enantiomers of disopyramide in human subjects (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 335-356 
    Details
    ISSN: 1573-8744
    Schlagwort(e): disopyramide ; pharmacokinetics ; stereoisomers ; antiarrhythmic agents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Disopyramide, an antiarrhythmic agent, is marketed as a racemic mixture of two enantiomers. The racemic drug has unusual pharmacokinetic properties because of its concentration-dependent binding to plasma proteins in the therapeutic plasma concentration range. This study examined, in healthy subjects, the individual pharmacokinetic properties of both total and unbound d-and ldisopyramide in plasma after intravenous administration of each enantiomer separately (1.5mg/kg).Also investigated is the pharmacokinetics of total d-and l-disopyramide in plasma after intravenous administration of a pseudoracemate. Both d-and l-disopyramide are found to exhibit concentration-dependent binding to plasma proteins, with d-disopyramide being more avidly bound at lower concentrations. The stereoselective, concentration-dependent binding to plasma proteins resulted in distinct pharmacokinetic properties when the enantiomers were given together as the pseudoracemate. d-Disopyramide had a lower plasma clearance and renal clearance, a longer half-life, and a smaller apparent volume of distribution than l-disopyramide. However, when the enantiomers were administered separately, there were no differences in the clearance, renal clearance, and volume of distribution between enantiomers calculated from either total or unbound drug concentrations. The results reveal an important pharmacokinetic interaction between the enantiomers of disopyramide when given as a racemic mixture, which may be dose-dependent and is not apparent upon administration of the enantiomers separately.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01059195
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  • 125
    Digitale Medien
    Digitale Medien
    The impact of neglecting nonlinear plasma-protein binding on disopyramide bioavailability studies (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 365-379 
    Details
    ISSN: 1573-8744
    Schlagwort(e): disopyramide ; bioavailability ; protein binding ; nonlinear ; sustained release ; pharmacokinetics ; ultrafiltration ; immunoassay
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Disopyramide has nonlinear protein binding and thus the relationship between the extent of its bioavailability and AUC,the area under the plasma concentration-time curve, is (1) nonlinear and (2) absorption rate-dependent. The unbound species follows linear pharmacokinetics. A solution of disopyramide, the innovator's product, and two generic formulations were found to be statistically indistinguishable in their bioavailability of disopyramide, whether comparison was based upon AUCor area under the plasma unbound concentration-time curve (AUCu).The AUCand AUCugave similar results because of truly similar bioavailability, coupled with sufficiently similar release rates, among the four preparations chosen for study. The concentration dependence of disopyramide protein binding and the time course of unbound plasma concentrations were fit by models which then allowed prediction of AUCunder various biopharmaceutical scenarios. Nonlinear binding of disopyramide to plasma proteins renders AUCan insensitive parameter for the discrimination of products with different extents of bioavailability; immediate release products allowing bioavailabilities of 75 or 125% relative to the solution can generate AUCs86 and 112%, respectively, of that from the solution. Nonlinear binding, furthermore, leads to a tendency for AUC tooverestimate the bioavailability of slower release products in single-dose studies; if AUCwere the index of bioavailability, products permitting the same bioavailability as the solution but releasing over 12 hr could appear to allow 114% relative bioavailability. Moreover, in some situations the bias arising from the insensitivity of AUCto product differences can be reinforced by the dependence of AUCon release rate; an apparent relative bioavailability of 80% can be achieved by a 12-hr release product allowing a true relative bioavailability of a mere 58%. While multiple-dose studies appear largely to avoid the tendency to overestimate low bioavailability in slow-release products, in these studies AUCappears to be even more insensitive in resolving discrepancies between products. Assay technology now available makes AUCua feasible and more reliable index of bioavailability than AUCwhen plasma protein binding of drugs is nonlinear.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01059197
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  • 126
    Digitale Medien
    Digitale Medien
    On the pharmacokinetics of 16-acetyl-gitoxin and its bioavailability from pengitoxin-containing tablet formulations (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 357-364 
    Details
    ISSN: 1573-8744
    Schlagwort(e): 16-acetyi-gitoxin ; pengitoxin ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract In six volunteers the pharmacokinetics of 16-acetyI-gitoxin (16AG, 0.5mg) administered intravenously (A1) and as an oral solution (A2) and of pengitoxin (PAG, 0.6 mg) administered intravenously (A3) was evaluated. In six volunteers the bioavailability of 16AG from two PAG tablet formulations (1.2 mg) (B2, B3) was measured by comparison with the absorption after administration of a pengitoxin solution (1.2mg) (B1). In both studies the test was performed using a crossover design. After a single i.v. injection of equimolar doses, 16AG and PAG showed similar mean kinetic parameters: t 1/2 =51.6hr (16AG) and 60.8 hr (PAG), CL=11.7ml min−1 (16AG) and 12.7ml min−1 (PAG), CLR=4.1 ml min−1 (16AG) and 4.2ml min−1 (PAG). The 16AG was absorbed from solution with a mean half-life of 0.2hr to an extent of 98.6%. The mean urinary excretion /Ae(0, 4)/ of 16AG amounted to 24.6% (A1), 20.8% (A2) and 28.1% (A3). On the basis of AUCvalues, the mean bioavailability of PAG from either tablet formulation amounted to 79.6% (B2) and 89.6% (B3). The pharmacokinetic parameters of 16AG (PAG) are closer to those of digitoxin than those of digoxin. In general, 16AG is characterized as a digitoxin with a digoxin-like elimination half-life.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01059196
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  • 127
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of isosorbide dinitrate and its mononitrate metabolites after intravenous infusion (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 1-17 
    Details
    ISSN: 1573-8744
    Schlagwort(e): isosorbide dinitratekw]isosorbide 2-mononitrate ; isosorbide 5-mononitrate ; metabolism ; pharmacokinetics ; modeling ; simultaneous estimation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Plasma concentrations of isosorbide dinitrate (ISDN) and its two active metabolites 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) have been measured during and for 6 hr after intravenous infusion at a rate of 2.5mg/hr during 1.75 hr in six cardiac patients, by a capillary gas chromatographic method. Data were analyzed by simultaneous modeling of the observed kinetics of the three compounds. Two or three phases were detected on the postinfusion ISDN concentration-time curves. ISDN concentrations declined with a mean terminal half-life of 2.81 hr±0.7 SD. The mean systemic clearance of ISDN (2.9 L/min ±0.7 SD) and its mean total volume of distribution (259 L +- 48 SD) were relatively high. Plasma 5-ISMN concentrations were 5- to 6-fold greater than those of 2-ISMN during the whole observation period. Maximum levels of 2-ISMN (6.7 ng/ml ± 0.9 SD) and of 5-ISMN (27 ng/ml ± 6 SD) occurred within a few minutes after the end of infusion. The mean half-lives of 2-ISMN (1.59 hr± 0.19 SD) and of 5-ISMN (3.78 hr± 0.79 SD) estimated by the model were smaller than those calculated by a model-independent method (2.95 hr± 0.41 SD and 5.98 hr± 2.22, respectively), but were in good agreement with those reported in the literature following separate administration of both metabolites to man. This study shows how such modeling can distinguish between metabolite formation and elimination processes and allow the determination of metabolite half-lives after administration of the precursor drug.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01059280
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  • 128
    Digitale Medien
    Digitale Medien
    Physiological pharmacokinetic modeling ofcis-dichlorodiammineplatinum(II) (DDP) in several species (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 131-155 
    Details
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; physiological model ; cisplatin ; DDP ; cis-dichlorodiammineplatinum(II)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A physiological pharmacokinetic analysis ofcis-dichlorodiammineplatinum(II) (DDP) is presented for the rabbit, dog, and human. The results are compared to a previous analysis for the rat. DDP binds irreversibly to low-molecular weight nucleophiles and macromolecules to form mobile and fixed metabolites at rates which are tissue-specific. The rate constant for the formation of fixed metabolite in plasma, determined by in vitro incubation, ranges from 0.004 to 0.008 min−1.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01065258
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  • 129
    Digitale Medien
    Digitale Medien
    Receptor-mediated model relating anticonvulsant effect to brain levels of camazepam in the presence of its active metabolites (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 309-321 
    Details
    ISSN: 1573-8744
    Schlagwort(e): camazepam ; temazepam ; oxazepam ; pharmacokinetics ; anticonvulsant effect ; radioreceptor assay ; rat ; mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract In a displacement test using3H-diazepam as a radioligand, the in vitro affinities of metabolites of camazepam (CZ) for the benzodiazepine receptors were 1–50 times more potent than that of CZ. In contrast, only three metabolites (temazepam, oxazepam, and hydroxy CZ), as well as CZ itself, exhibited an in vivo affinity parallel to their ability to protect against pentylenetetrazole-induced clonic convulsion in rats. In addition, CZ and these active metabolites displaced the radioligand from their receptor sites in a concentration-dependent saturable manner, indicating the competitive bimolecular interaction of these molecules with their receptors. The percent anticonvulsant effect was a nonlinear, single-valued function of the in vivo percent displacement of specific3H-diazepam binding, independent of these displacers after i.v. dosing; this relationship could be approximated by the Hill equation. On the basis of these findings, a receptor-mediated model, including the Langmuir equation to describe the receptor binding-brain concentration relationship and the Hill equation to accommodate the anticonvulsant effect-receptor binding relationship, was constructed. This model was found to adequately relate the time course values of anticonvulsant effect and of brain levels of CZ and its active metabolites after oral administration. These results demonstrate that CZ and its active metabolites exert anticonvulsant effect by competitive binding to the benzodiazepine receptors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01106709
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  • 130
    Digitale Medien
    Digitale Medien
    Effect of caffeine on ceftriaxone disposition and plasma protein binding in the rat (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 397-408 
    Details
    ISSN: 1573-8744
    Schlagwort(e): caffeine ; ceftriaxone ; plasma ; tissue ; pharmacokinetics ; compartment model ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Previous studies have shown that caffeine can affect drug kinetics by altering drug binding to plasma protein, drug absorption, or drug distribution. In this study, the effect of caffeine on the in vivoprotein binding and the disposition of ceftriaxone (a highly protein-bound cephalosporin) were investigated in the rat. Ceftriaxone 100mg/kg and caffeine 20mg/kg were i.v. injected via the tail vein and ceftriaxone in plasma, plasma filtrate, urine, feces, and tissues (brain, heart, kidney, liver, gut, lung, and muscle) was assayed by HPLC with UV detection. The fraction of free ceftriaxone in plasma ranged from 5.6 to 32.8% of total ceftriaxone (3–347 μg/ml) without caffeine and showed no alteration by caffeine. The total amount of ceftriaxone excreted in urine and feces was increased significantly (p〈0.05)from 13.1±1.8mg (mean±SD, 54.6% of total) to 15.3 ±1.1 mg (63.8% of total) by caffeine coadministration. The terminal half-life of ceftriaxone in plasma was shortened from 59 to 47 min, and the area under the plasma drug concentration-time curve (AUC)was reduced from 612 to 516 μg hr/ml Although the peak drug concentrations and the times of peak concentration of ceftriaxone in tissues were not altered by caffeine administration, the elimination of ceftriaxone was increased, as indicated by generally shorter half-lives (decreases ranged from 17.5% in liver to 34.2% in brain) and lower AUCvalues (from 9.0% in heart to 54.5% in brain). These results suggest that caffeine does not alter the protein binding of ceftriaxone, but enhances the elimination of ceftriaxone in the rat.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01059199
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  • 131
    Digitale Medien
    Digitale Medien
    Drug pharmacokinetics and the carbon dioxide breath test (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 29-49 
    Details
    ISSN: 1573-8744
    Schlagwort(e): carbon dioxide ; breath test ; pharmacokinetics ; metabolite ; extraction ratio ; aminopyrine ; caffeine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The interrelationship of the pharmacokinetics of a drug and the expiration of carbon dioxide formed as a metabolite have been studied. The pharmacokinetic characteristics of the drug that affect the usefulness of the carbon dioxide excretion as a measure of liver function were examined by means of computer simulations. The parent drug extraction ratio, fraction demethylated, volume of distribution, and absorption rate of an oral dosage form all contribute to the carbon dioxide breath test result. A drug that would be a useful substrate when the carbon dioxide breath test is used as a probe for changes in liver function should be at least 50% metabolized by demethylation, have a hepatic extraction ratio of 0.2–0.5, and be administered in a form that is rapidly absorbed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01059282
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  • 132
    Digitale Medien
    Digitale Medien
    Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous furosemide (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 495-509 
    Details
    ISSN: 1573-8744
    Schlagwort(e): furosemide ; pharmacokinetics ; pharmacodynamics ; fluid replacement
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of furosemide were evaluated using the dog as a model animal. Each of six dogs received 8-hr constant intravenous infusion of 20 mg (15 mg used in one dog) of furosemide with 0% replacement (treatment I), 50% replacement (treatment II), and 100% replacement (treatment III) with lactated Ringer's solution, as well as with 100% replacement with 5% dextrose in water (treatment IV). Most pharmacokinetic parameters, such as plasma clearance, steady-state volume of distribution, mean residence time, and terminal half-life, were essentially the same in all four treatments. Renal clearances and urinary excretion rates of the drug in treatments II–IVwere essentially the same, but about 20% higher than those in treatment I.In spite of the similarities in kinetic properties, diuretic and/or natriuretic effects from furosemide were markedly different among the four treatments. For example, mean 10-hr urine outputs were 646, 1046, 3156, and 1976 ml and mean 10-hr sodium excretions were 87.0, 142, 383, and 97.2 mmole for treatments I–IV,respectively. Except for treatment III,diuresis and/or natriuresis were found to be time-dependent, generally decreasing with time until reaching a low plateau during later hours of infusion. The present findings also showed that (1)no fluid replacement and 100% replacement with 5% dextrose solution both produced the same degree of severe acute tolerance in natriuresis, indicating the insignificance of water compensation in tolerance development; (2)in treatment II,where neutral sodium balance was achieved, the development of acute tolerance in diuresis and natriuresis can mainly be attributed to negative water balance under this special condition; (3)at steady state the hourly diuresis and natriuresis could differ up to about ten times between treatments. Some implications for the kinetic/dynamic relationship or modeling, in the clinical use, and in the bioequivalence evaluation of dosage forms are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01059657
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  • 133
    Digitale Medien
    Digitale Medien
    Amiodarone pharmacokinetics. I. Acute dose-dependent disposition studies in rats (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 601-613 
    Details
    ISSN: 1573-8744
    Schlagwort(e): amiodarone ; pharmacokinetics ; dose-dependent ; rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Single intravenous bolus doses of amiodarone hydrochloride of 30, 60, 90 and 120 mg/kg were administered to male Sprague-Dawley rats to determine the effects of dose on amiodarone pharmacokinetics. Serial blood samples and total urine were collected over 48 hr and assayed for amiodarone and desethylamiodarone by HPLC. The blood amiodarone concentration-time curves for the four doses were best described by a triexponential equation with terminal half-lives (t 1/2γ ) ranging from 17 to 20 hr. Over the dose range studied, no changes in γ, t 1/2γ , or central compartment volume (Vc=1.2–1.4 L/kg) were observed. On the other hand, reductions in amiodarone clearance (CL and steady-state volume of distribution (V ss of 44% (17.7 to 10.0 ml/min per kg) and 50% (16.4 to 8.2 L/kg), respectively, were noted as the dose of amiodarone increased. The conversion of amiodarone to desethylamiodarone (fm was dose-independent and amounted to approximately 10% of each amiodarone dose. No amiodarone or desethylamiodarone was detected in the urine of any of the treated animals. The blood-to-plasma concentration ratio of amiodarone was concentration-independent and therefore did not account for the dose-dependent changes in Vss and CL observed. The data suggested that the dose-dependent changes noted were due to an alteration in the volume (s) of the peripheral tissue compartment(s).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01067966
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  • 134
    Digitale Medien
    Digitale Medien
    Analysis of pethidine disposition in the pregnant rat by means of a physiological flow model (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 381-395 
    Details
    ISSN: 1573-8744
    Schlagwort(e): pethidine ; rat ; physiological flow model ; pharmacokinetics ; pregnancy ; scale up ; opiates, GC-MS analytical method ; simulations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The disposition of pethidine (meperidine) in the pregnant rat is described by means of a physiological flow model. The model includes arterial and venous blood, brain, fat, fetal, hepatic, intestinal, muscular, pulmonar, and renal tissues. The concentration-time profiles of pethidine calculated by the model are consistent with experimental data, except for the brain and renal tissues, where the model predicts initially higher concentrations. Simulations are carried out to further explore the contribution from different organs on the kinetics in blood and tissues. The tissue-to-blood partition coefficients vary over a range from 5 to 316, where fat has the lowest and liver the highest after a correction is made due to hepatic extraction. Rapid uptake occurs into highly perfused organs such as brain, kidneys, liver, and lungs, followed by fetus, intestines, muscle, and fat. Data indicate no marked membrane resistance to pethidine of the investigated organs, except for fetal tissues, but rather a perfusion-limited uptake. Simulations suggest that muscles and adipose tissue play an important role in the rat, becoming the major reservoir of drug during the intermediate and terminal elimination phase, respectively. Volume of distribution and the biological half-life agree with reported findings. Pethidine is subject to a high systemic blood clearance, which exceeds the total hepatic blood flow in the rat. No degradation of pethidine is found in blood, and therefore a pulmonary expression for pethidine clearance is added as a potential source of pethidine elimination. The elimination of pethidine after a single i.v. bolus dose is found to be dependent on simulated changes in cardiac output and hepatic blood flow. A simulation is performed with the scaled model to mimic the human concentration-time profiles in maternal blood and brain tissues and fetal tissue during repetitive doses of pethidine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01059198
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  • 135
    Digitale Medien
    Digitale Medien
    Saturable Processes Affecting Renal Clearance of Cefixime in Dogs (1986)
    Springer
    Pharmaceutical research 3 (1986), S. 150-155 
    Details
    ISSN: 1573-904X
    Schlagwort(e): renal clearance ; cephalosporin ; cefixime ; tubular reabsorption ; saturable protein binding ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The pharmacokinetics of cefixime, a new orally active cephalosporin, was studied after an intravenous dose of 50 mg/kg to four beagle dogs. Cefixime was shown to exhibit concentration dependent serum protein binding and saturable tubular reabsorption. The drug was excreted mainly in the urine, the net result of glomerular filtration and saturable tubular reabsorption. The experimental results were analyzed by model independent pharmacokinetic equations and with theoretical models describing renal clearance. Modification of the models, based on observed data, was proposed. The experimental methods employed and the pharmacokinetic approach offered in this study can be applied to drugs that exhibit concentration dependent protein binding and saturable renal elimination processes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016309923717
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  • 136
    Digitale Medien
    Digitale Medien
    The Effect of Amiodarone on Theophylline Pharmacokinetics in the Rat (1986)
    Springer
    Pharmaceutical research 3 (1986), S. 167-169 
    Details
    ISSN: 1573-904X
    Schlagwort(e): amiodarone ; theophylline ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Amiodarone is an investigational antiarrhythmic agent which has been implicated in reducing the activity of the hepatic mixed-function oxidase system. To evaluate this effect further, two groups of six male Sprague–Dawley rats each received theophylline (6 mg/kg, iv) preceded by either normal saline or amiodarone HC1 (100 mg/kg, iv). Blood samples were obtained serially for a period of 6 hr and the sera were assayed for theophylline by high-pressure liquid chromatography (HPLC). In rats pretreated with amiodarone, a significant 45% reduction in the mean (± SD) systemic clearance [0.057 (0.010) vs 0.031 (0.004) liter/hr/kg, P 〈 0.001] and a greater than 100% increase in the mean elimination half-life [2.03 (0.46) vs 4.29 (0.71) hr, P 〈 0.001] of theophylline were observed. These data demonstrate an acute inhibitory effect of amiodarone on the hepatic microsomal enzyme system.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016366008696
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  • 137
    Digitale Medien
    Digitale Medien
    Engineering Targeted In Vivo Drug Delivery. I. The Physiological and Physicochemical Principles Governing Opportunities and Limitations (1986)
    Springer
    Pharmaceutical research 3 (1986), S. 333-344 
    Details
    ISSN: 1573-904X
    Schlagwort(e): drug delivery, targeted ; prodrugs ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A physiologically based model is presented to aid prediction of the pharmacological benefits to be derived from the administration of a drug as a targeted drug–carrier combination. An improvement in the therapeutic index and an increase in the therapeutic availability are the primary benefits sought. A measure of the former is obtained from the value of the drug targeting index, a newly derived parameter. Both the drug targeting index and the therapeutic availability are directly calculable. The minimum information needed for approximating both parameters is the candidate drug's total-body clearance and some knowledge of the target site's anatomy and blood flow. Drugs with high total-body clearance values that are known to act at target tissues having effective blood flows that are small relative to the blood flow to the normal eliminating organs will benefit most from combination with an efficient, targeted carrier. Direct elimination of the drug at the target site or at the tissue where toxicity originates dramatically improves the drug targeting index value. The fraction of drug actually released from the carrier at both target and nontarget sites can radically affect index values. In some cases a 1% change in the fraction of the dose delivered to the target can result in a 50% change in the drug targeting index value. It is argued that most drugs already developed have a low potential to benefit from combination with a drug carrier. The approach allows one to distinguish clearly those drugs that can benefit from combination with targeted in vivo drug carriers from those drugs that cannot.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016332023234
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  • 138
    Digitale Medien
    Digitale Medien
    Influence of Malnutrition on the Disposition of Metronidazole in Rats (1986)
    Springer
    Pharmaceutical research 3 (1986), S. 352-355 
    Details
    ISSN: 1573-904X
    Schlagwort(e): malnutrition ; metronidazole ; pharmacokinetics ; rats ; metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The influence of dietary protein deficiency on the disposition of metronidazole and its two major metabolites was examined in male Sprague–Dawley rats fed for 4 weeks on a 23% (control-) or a 5% (low-) protein diet ad libitum. Following an intravenous bolus dose of 10 mg/kg metronidazole hydrochloride, blood samples were obtained serially for a period of 24 hr after drug administration. Serum concentration–time data were analyzed by nonlinear least-squares regression, as well as noncompartmental techniques. The average mean residence time (MRT) was significantly prolonged by 48%, while the systemic clearance (Cl) was decreased by 42% in the protein-deficient rats. Since there was no alteration in the apparent steady-state volume of distribution (V ss), the mean harmonic half-life was increased from 2.9 to 5.0 hr in the protein-deficient rats. Although the percentage of metronidazole recovered as total drug in the urine over 24 hr was not significantly different between the two groups of animals, rats on a low-protein diet excreted a significantly smaller percentage of the administered dose as unchanged metronidazole (mean ± SD, 24.6 ± 3.8 vs 36.5 ± 12%) and a larger percentage (16.7 ± 2.6 vs 8.3 ± 1.8%) as the hydroxylated metabolite. No significant difference in the partial metabolic clearance of the hydroxylated metabolite of metronidazole was seen between the two groups of animals; however, there was a significant decrease in the renal clearance of metronidazole (1.45 ± 0.68 vs 0.55 ± 0.06 ml/min/kg) in the rats fed a low-protein diet. We conclude that the decreased clearance of metronidazole in protein deficiency is a result primarily of the decreased glomerular filtration rate, decreased biliary excretion, and/or increased net tubular reabsorption of metronidazole.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016433724142
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  • 139
    Digitale Medien
    Digitale Medien
    Bioavailability of Propranolol After Oral, Sublingual, and Intranasal Administration (1986)
    Springer
    Pharmaceutical research 3 (1986), S. 108-111 
    Details
    ISSN: 1573-904X
    Schlagwort(e): propranolol ; intranasal ; sublingual ; absorption ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The bioavailability of propranolol was compared after oral, sublingual, and intranasal administration in eight healthy male volunteers. Relative to the bioavailability after intranasal (in) administration, which was previously shown to be nearly complete (F relin = 100%), the sublingual (sl) administration of a standard 10-mg tablet gave a bioavailability of F relsl = 63 ± 22%, while the oral (or) administration yielded only F relor = 25 ± 8%. The serum concentration–time curves of propranolol after sublingual administration resembled those of a sustained-release preparation. This sustained-release phenomenon after the sublingual route is reflected in the mean residence times (MRTs) of propranolol in the body (MRTor = 5.7 ± 1.3 hr, MRTsl - 6.4 ± 1.3 hr, MRTin = 4.6 ± 1.0 hr; mean ± SD; N = 8). MRTs after sublingual administration were significantly longer than after the oral and the intranasal doses (P 〈 0.05 and P 〈 0.002, respectively).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016345504153
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  • 140
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and Reversible Biotransformation of Sulfinpyrazone and Its Metabolites in Rabbits. I. Single-Dose Study (1986)
    Springer
    Pharmaceutical research 3 (1986), S. 173-177 
    Details
    ISSN: 1573-904X
    Schlagwort(e): sulfinpyrazone ; pharmacokinetics ; reversible metabolism ; single dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract In rabbits receiving sulfmpyrazone (SO) and the sulfide metabolite (S) in four separate experiments, the biotransformation of SO into S was found to be reversible, which resulted in approximately parallel terminal disposition profiles for the three major substances in plasma, i.e., SO, S, and the p-OH-sulfide (OH-S). However, differences in disposition kinetics were observed between the intravenous and the peroral administration. The formation of OH-S was independent of both the administered compound and the administration route. The results obtained in the present studies, the previously documented enterohepatic recirculation, and the formation of S by hindgut flora may have implications for studies on sulfinpyrazone, which has been used as an antithrombotic agent.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016370209604
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  • 141
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and Reversible Biotransformation of Sulfinpyrazone and Its Metabolites in Rabbits. II. Multiple-Dose Study (1986)
    Springer
    Pharmaceutical research 3 (1986), S. 178-183 
    Details
    ISSN: 1573-904X
    Schlagwort(e): sulfinpyrazone ; pharmacokinetics ; reversible metabolism ; multiple dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract In crossover studies rabbits were given sulfmpyrazone (SO) and its sulfide metabolite (S) perorally once daily (10 mg/kg) for 5 days. Comparison of the pharmacokinetic parameters obtained after the first and the fifth dose indicates that repeated dosing does not alter disposition kinetics of both SO and S, except that in dosing with S the observed terminal half-life for S is significantly reduced, from 4.59 ± 0.55 to 2.86 ± 0.6 hr (SD). In other studies rabbits were given higher single doses (15, 25, and 50 mg/kg) perorally and comparison was made between these dose sizes and the first dose (10 mg/kg) of multiple administration with S. Some kinetic parameters tended to be altered in a nonlinear fashion, and greater intersubject variations were observed because of the dose increase, while oxidation to SO or p-hydroxylation to OH-S from S was not significantly altered.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016322326443
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  • 142
    Digitale Medien
    Digitale Medien
    Pharmacoclinical data on high dose medroxyprogesterone acetate in advanced breast cancer (1986)
    Springer
    Breast cancer research and treatment 8 (1986), S. 161-163 
    Details
    ISSN: 1573-7217
    Schlagwort(e): medroxyprogesterone acetate ; pharmacokinetics ; response ; toxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01807705
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  • 143
    Digitale Medien
    Digitale Medien
    Phase I clinical and pharmacokinetic study of bisantrene in refractory pediatric solid tumors (1986)
    Springer
    Investigational new drugs 4 (1986), S. 149-153 
    Details
    ISSN: 1573-0646
    Schlagwort(e): bisantrene ; Phase I ; pharmacokinetics ; pediatric solid tumors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Fourteen patients with pediatric malignant solid tumors, median age 15 years, received 22 courses of bisantrene in a Phase I study. Dosage escalations ranged from 10 to 120 mg/m2 daily for 5 consecutive days. Toxicity included myelosuppression and phlebitis. A sensitive (detection limit of 2 ng/ml) and specific HPLC method was developed to quantitate bisantrene in patient's plasma and urine. Peak plasma concentrations at the end of 60 minute infusions ranged from 568 ng/ml at 10 mg/m2 to 6800 ng/ml at the 100 mg/m2 dosage. The elimination half life (T 1/2β) averaged about 10 hours but increased to 20 hours in a patient with liver disease. Only 2.4–10% of the bisantrene dose was eliminated in the urine suggesting that the liver may be the major route of elimination for this antineoplastic anthracene derivative.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00194594
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  • 144
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of intravenous glibenclamide investigated by a high performance liquid Chromatographic assay (1982)
    Springer
    Diabetologia 23 (1982), S. 37-40 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Glibenclamide ; pharmacokinetics ; high performance liquid chromatography ; plasma insulin ; blood glucose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A simple high performance liquid Chromatographic assay for the determination of plasma glibenclamide concentrations is described. This resolved glibenclamide from normal plasma constituents. The calibration curve of the assay was linear over the range 10–500 μg/1 and the minimum level of detection was 2 μg/1. Within-assay coefficients of variation were 11.6% (20 μg/1); 5.3% (50 μg/1); 6.8% (100 μg/1); between-assay coefficients of variation were 8.4% (20 μg/1); 4.7% (50 μg/1) and 7.4% (100 μg/1). The assay was used to study the pharmacokinetics of a 1 mg intravenous dose of glibenclamide in eight normal subjects. The mean half-life was found to be 1.47±0.42 h (SD) and no evidence for a non-linear β-phase or slowly equilibrating ‘deep’ compartment was found although this could not be rigorously excluded. The mean systemic drug clearance was 78±29 ml·h-1·kg-1 and the apparent volume of distribution in the β-phase was 155±44 ml/kg. The median time of maximum response of plasma immunoreactive insulin was 25 min and the median time of maximum blood glucose response was 53 min. No correlation could be found between the pharmacokinetics of glibenclamide and these responses in fasted normal individuals.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00257728
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  • 145
    Digitale Medien
    Digitale Medien
    The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide in essential hypertensives (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 287-291 
    Details
    ISSN: 1432-1041
    Schlagwort(e): tolmesoxide ; hypertension ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined β-blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637615
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  • 146
    Digitale Medien
    Digitale Medien
    Kinetics of a high dose of piretanide in renal failure (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 307-310 
    Details
    ISSN: 1432-1041
    Schlagwort(e): piretanide ; renal failure ; high dose ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of piretanide was studied in patients with renal failure. After oral administration of a high dose of piretanide (96 mg), the pharmacokinetic parameters were: elimination rate constant 0.346±0.072 h−1, half life 2.00±0.35 h, and total plasma clearance 119.55±35.90 ml · min−1. Compared to the values obtained in adults with normal renal function, these results show a decrease in total plasma clearance, but conservation of the metabolic clearance which amounts to 45% of the total clearance in the healthy adult.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637618
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  • 147
    Digitale Medien
    Digitale Medien
    Correlation between pharmacokinetics and clinical effects of ergotamine in patients suffering from migraine (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 397-402 
    Details
    ISSN: 1432-1041
    Schlagwort(e): ergotamine ; migraine ; radioimmunoassay ; clinical effects ; adverse effects ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic availability of ergotamine after a single therapeutic oral or rectal dose was studied using a radioimmunoassay during the headachefree state in 24 patients suffering from migraine. Plasma concentrations of the drug were compared with anamnestic data about its clinical effects in the same patients. Among 12 patients with a good therapeutic response to medication, the mean plasma ergotamine levels stayed in the range 0.20 to 0.50 ng/ml for 6h. Their mean plasma levels at 30 min (0.33ng/ml) and 1h (0.40ng/ml) were significantly higher than those (0.06 and 0.08ng/ml, respectively) in 9 patients with only a moderate therapeutic response. In 9 patients with a moderate and 3 with a poor therapeutic response, the mean plasma level generally stayed below 0.10ng/ml. The mean peak concentrations in moderate (0.13 ng/ml) and poor (0.11ng/ml) responders appeared later (at 3h) than in good responders (at 1h). Side effects of the medication appeared to be associated with relatively low plasma levels of ergotamine and also with delayed maximum plasma concentrations of the drug. The present results suggest that the time of the maximum plasma drug level is an important determinant of the clinical effects of ergotamine, and that a good therapeutic response may be expected if a plasma ergotamine level of 0.20ng/ml or more is achieved within 1 hour after oral or rectal administration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542326
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  • 148
    Digitale Medien
    Digitale Medien
    Difference between single and multiple dose pharmacokinetics of orphenadrine hydrochloride in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 343-350 
    Details
    ISSN: 1432-1041
    Schlagwort(e): orphenadrine ; single dose ; multiple doses ; bioavailability ; pharmacokinetics ; N-demethylorphenadrine ; metabolism ; dog ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations of orphenadrine were measured by a specific gaschromatographic method in 5 healthy male volunteers after a single oral dose of orphenadrine hydrochloride 100mg. The single dose pharmacokinetic profile of orphenadrine was evaluated from these data. The elimination half-life ranged from 13.2–20.1 h after the commercial tablet formulation. Plasma concentrations, determined in volunteers and patients under different conditions of repeated oral administration of the same formulation of orphenadrine hydrochloride exceeded the theoretical values, predicted from the single dose pharmacokinetics, by a factor 2 to 3. The elimination half-lives after discontinuation of treatment showed a 2 to 3-fold increase over the single dose values. This demonstrates a clear discrepancy between the multiple and single dose pharmacokinetics of orphenadrine. Experiments in dogs suggested competition for biotransformation between orphenadrine and its metabolite N-demethylorphenadrine. Product inhibition of this type could explain the observed discrepancy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637624
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  • 149
    Digitale Medien
    Digitale Medien
    Comparative pharmacokinetic analysis of amoxycillin using open two and three-compartment models (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 273-279 
    Details
    ISSN: 1432-1041
    Schlagwort(e): amoxycillin ; i.v. administration ; pharmacokinetics ; two- and three-compartment models
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic characteristics of amoxycillin were studied in healthy volunteers after intravenous injection of 250 mg, 500 mg and 1,000 mg, and infusion of 2 g and 5 g. Serum concentrations were fitted using either bi- and tri- exponentional equations. Comparison of the regression curves obtained revealed that the three-compartment model gave a better fit to the serum concentration versus time curve. It was evident that there was a third, slow, dose dependent phase of disposition. This result has been confirmed by the fact that the terminal half life of amoxycillin on cessation of a continuous infusion is significantly greater than after acute administration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00545227
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  • 150
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and bioavailability of indapamide — A new antihypertensive drug (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 295-299 
    Details
    ISSN: 1432-1041
    Schlagwort(e): indapamide ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Two formulations of indapamide tablets (2.5 mg) were given as a 5.0 mg dose and the subsequent blood levels were compared to those obtained after administration of a 5.0 mg solution. The study was conducted as a randomized three-way crossover design using healthy male volunteers. The drug was well tolerated by all the subjects involved. The area under the blood concentration versus time curve, extrapolated to infinity was essentially the same for all three formulations (4.2, 4.7, and 4.4 µg-h/ml). Statistical comparison of the blood levels from the two tablets showed that one tablet had a significantly greater maximum blood concentration (263 vs 231 ng/ml) and a significantly shorter time of maximum blood concentration (2.3 vs 3.5 h). Cmax (333 ng/ml) and tmax (0.7 h) values for the solution were significantly higher than either tablet. The average half-life (β-phase) for all three formulations was 15 h, while the average systemic clearance was 20 ml/min. Indapamide has a low clearance rate and there was no evidence that the drug undergoes a first-pass effect.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548396
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  • 151
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of TRIS (hydroxymethyl-)aminomethane in healthy subjects and in patients with metabolic acidosis (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 257-264 
    Details
    ISSN: 1432-1041
    Schlagwort(e): TRIS buffer ; metabolic acidosis ; pharmacokinetics ; cellular uptake ; renal excretion ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To investigate the pharmacokinetics of TRIS, an infusion of the buffer was given to 6 healthy volunteers (121 mg/kg=1 mmol/kg; pH 7.4) and to 20 patients suffering from metabolic acidosis (109–376 mg/kg; pH 10.9). The drug exhibited two-compartment characteristics in volunteers (t0.5,β=5.6 h) and patients with intact renal function (t0.5,β=16.3–45.6 h). The final volume of distribution (Vβ) indicated uptake into tissues, but equilibration between body compartments was slow. Mainly unchanged TRIS was eliminated by the kidney; 82% of the administered dose was recovered from 24 h-urine of healthy subjects. In the patients a linear correlation between creatinine-clearance and TRIS-clearance was observed, the latter always being somewhat greater than the former. Only insignificant amounts of the drug were found in bile and gastric juice. In anuric patients the plasma concentration of TRIS declined monoexponentially, with a half-life between 10 and 58 h. Haemodialysis or haemofiltration did not influence this process. From the data it seems questionable whether cellular uptake of TRIS is an important factor in the therapy of intracellular acidosis, but the possibility of drug accumulation must be borne in mind if repeated doses are given to the same patient.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00545225
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  • 152
    Digitale Medien
    Digitale Medien
    Influence of food on the kinetics of 8-methoxypsoralen in serum and suction blister fluid in psoriatic patients (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 75-80 
    Details
    ISSN: 1432-1041
    Schlagwort(e): psoriasis ; 8-methoxypsoralen ; food influence ; suction blister fluid ; serum ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of food on the kinetics of 8-methoxypsoralen (8-MOP) in serum and suction blister fluid was evaluated in a cross-over study in 19 psoriatic patients under PUVA treatment. The peak serum concentration of 8-MOP was reached 1.5 h after ingestion on an empty stomach, and in suction blister fluid the maximum concentration was already present in the first sample taken after 2 h, the time when UVA radiation was given. The postprandial kinetics of 8-MOP in serum and suction blister fluid differed, the highest levels being reached, respectively, at 2.4 and 3 h after intake, i.e. in both body fluids after irradiation had started. The side effects of 8-MOP, such as nausea and dizziness, in the two groups were similar. The present results indicate that to optimize the therapeutic effect of PUVA in individual patients, 8-MOP should be given on an empty stomach.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01061380
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  • 153
    Digitale Medien
    Digitale Medien
    Clinical pharmacology of a new β-adrenoceptor blocking drug, befunolol (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 189-195 
    Details
    ISSN: 1432-1041
    Schlagwort(e): befunolol ; propranolol ; pharmacokinetics ; pharmacodynamic effects ; beta-adrenoceptor blocking agent
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Repeated doses of a new β-adrenoceptor blocking agent, befunolol, were administered orally to adult male volunteers for a cross-over comparison with propranolol. The β-adrenoceptor blocking activity of befunolol was greater than that of propranolol when assessed by the percentage reduction in exercise-induced tachycardia. The elimination half-life of drug was significantly prolonged on repeated administration of propranolol, but not of befunolol. The percentage reduction in exercise-induced tachycardia was highly correlated with the log plasma level of each drug. Both drugs produced a significant reduction in pre-exercise systolic and diastolic blood pressure, and significant attenuation of exercise-induced rise in systolic blood pressure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00547552
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  • 154
    Digitale Medien
    Digitale Medien
    Kinetics of ergotamine after intravenous and intramuscular administration to migraine sufferers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 235-240 
    Details
    ISSN: 1432-1041
    Schlagwort(e): ergotamine ; pharmacokinetics ; migraine ; plasma drug levels ; i.v. administration ; i.m. administration ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of ergotamine has been investigated in migrainous patients using a new, specific, sensitive HPLC assay (detection limit 100 pg/ml plasma). 10 patients were given ergotamine tartrate 0.5 mg i.v. and 5 of them received the same dose i.m. 2–3 weeks later. Blood samples were collected for up to 54 h following administration and the plasma concentration were analysed. After intravenous administration the plasma ergotamine declined rapidly, with an initial distribution half-life of 3 min followed by a mean terminal half-life of 1.86 h (range 90–155 min). The mean total plasma clearance was 11.0 ml kg−1 min−1, and the volume of distribution (Vdβ ) was 1847.6 ml kg−1. Individual t1/2β showed a positive linear correlation with the individual Vdβ . The intramuscular absorption of ergotamine was rapid and maximum plasma levels were usually obtained 10 min following administration. The biological availability was incomplete and variable at 46.6% (range 28.3–60.8%).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00547560
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  • 155
    Digitale Medien
    Digitale Medien
    Does cantharides blister fluid provide access to the peripheral compartment? (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 327-330 
    Details
    ISSN: 1432-1041
    Schlagwort(e): bendroflumethiazide ; cantharides plasters ; blister fluid ; plasma levels ; pharmacokinetics ; compartmental analysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of bendroflumethiazide (BFT) was investigated following the oral administration of 10 mg to 3 healthy volunteers. Each subject participated twice in the study. BFT was determined in plasma and cantharides blister fluid from 1/2 to 30 h post administration. Blister fluid was obtained from blisters 10–22 h old. Plasma levels were fitted to a tri-exponential equation and the concentration of the drug in the peripheral compartment was calculated from the microscopic rate constants. In 5 of 6 cases investigated, cantharides blister fluid levels paralleled the concentration of the drug in the peripheral compartment. The mean blister fluid levels exceeded the calculated concentration in Compartment 2 1.46 fold. In one case, the blister fluid level paralleled the plasma level. This subject clearly differed from the others as more than 10 h were required for blister formation in her. The results suggest that following the administration of BFT, cantharides blister fluid behaves as part of the peripheral compartment. The possible value of studying blister fluid levels in pharmacokinetic investigations is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613614
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  • 156
    Digitale Medien
    Digitale Medien
    The influence of free fatty acids on valproic acid plasma protein binding during fasting in normal humans (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 343-347 
    Details
    ISSN: 1432-1041
    Schlagwort(e): valproic acid ; fatty acids ; plasma protein binding ; pharmacokinetics ; drug metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of physiologic variations of free fatty acid levels on in vivo valproic acid plasma protein binding was studied in 6 healthy adult subjects. 14 blood samples were taken during a 12-h dosing interval at steady state while in a fed condition and also during a 27 h fast. Free fraction and total valproate concentration were determined by equilibrium dialysis and GLC, respectively. Free fatty acid levels were determined from both fresh samples and samples incubated at 37°C for 12 h, the latter in order to simulate equilibrium dialysis conditions. Fasting resulted in increased serum free fatty acid levels in all subjects, ranging from 34–182% (p〈0.01). Incubation also caused free fatty acid levels to rise, more so in fed samples (50–87%,p〈0.01) than in fasting samples (10–50%,p〈0.01). Fasting resulted in a 9% increase in the mean free fraction for all subjects combined (p〈0.01). Regression analysis of 180 sets of values for free fraction, total valproate concentration and free fatty acid level suggested that valproate concentration accounts for 17% and free fatty acid level for 37% of the variation in free fraction. Mean clearance was unchanged by fasting despite an increased free fraction suggesting decreased intrinsic clearance (i.e. decreased metabolism) of valproate under these conditions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613618
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  • 157
    Digitale Medien
    Digitale Medien
    Pharmacokinetic studies of oral L-threo-3,4-dihydroxyphenylserine in normal subjects and patients with familial amyloid polyneuropathy (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 463-468 
    Details
    ISSN: 1432-1041
    Schlagwort(e): L-threo-3,4-dihydroxyphenylserine ; familial amyloid polyneuropathy ; pharmacokinetics ; norepinephrine ; pressor response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of oralL-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, andL-threo-DOPS in plasma and urine was determined by high performance liquid chromatography with an electrochemical detector after separation on a boric acid gel column.L-threo-DOPS was slowly absorbed by normal subjects; the maximum plasma concentration occurred 3 h after administration and 20% of the oral dose was recovered unchanged in the urine within 12 h. It induced a substantial elevation of plasma norepinephrine levels, the peak being attained at 5 h, but without any change in blood pressure. In the patients, the absorption and metabolism ofL-threo-DOPS were delayed, and a prolonged pressor response was observed, with a peak after 8 h. It was concluded that the effects on plasma norepinephrine and blood pressure of oralL-threo-DOPS were essentially equal to those of twice as large a dose ofDl-threo-DOPS.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00605999
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  • 158
    Digitale Medien
    Digitale Medien
    Cimetidine dosage regimen for patients with renal failure and for geriatric patients (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 501-504 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; uraemia ; dosing regimen ; prediction ; computer program ; old age ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Using a recently developed computer program based on a correlation between methods to predict the elimination half-life and apparent volume of distribution of cimetidine and actual data from patients, ideal dosage regimens were generated for patients with renal impairment and for geriatric patients, together with the corresponding maximum and minimum steady state concentrations. Using the ideal dosage regimens, practical regimens with feasible dosing intervals of 6, 8 and 12 h were computed, which should result in therapeutic concentrations of 0.4 to 1.3 µg/ml. For uraemic patients and geriatric patients above the age of 75 years it would be desirable to have an additional oral 100 mg dosage form.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637496
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  • 159
    Digitale Medien
    Digitale Medien
    Overdosage of antidepressants: Clinical and pharmacokinetic aspects (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 513-521 
    Details
    ISSN: 1432-1041
    Schlagwort(e): amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637499
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  • 160
    Digitale Medien
    Digitale Medien
    Pharmacokinetic and pharmacodynamic studies of oral clonidine in normotensive subjects (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 1-5 
    Details
    ISSN: 1432-1041
    Schlagwort(e): clonidine ; noradrenaline ; pharmacokinetics ; arterial blood pressure ; plasma concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of clonidine and its relation to blood pressure response and side effects were studied after single oral doses of 75 µg, 150 µg and 250 µg in normotensive subjects. Following oral administration, the drug was absorbed rapidly after an initial lag time of 19–22 min and peak levels were reached between 2.4 and 2.9 h. Sampling over 48 h was necessary for accurate estimation of pharmacokinetic parameters. Post-peak plasma concentration declined in a monoexponential manner and the half-life of the elimination phase ranged from 9.0 to 15.1 h. Maximum plasma concentration (Cmax) and area under curve (AUC) increased proportionally with increasing doses. Clonidine produced significant reductions in the pulse rate and a dose dependent decrease in blood pressure. Clonidine (150 µg) also produced significant reductions in plasma catecholamine levels.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01061368
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  • 161
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of intravenous timolol in patients with acute myocardial infarction and in healthy volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 43-47 
    Details
    ISSN: 1432-1041
    Schlagwort(e): timolol ; pharmacokinetics ; pharmacodynamics ; healthy subjects ; cardiac infarction patients ; i.v. therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Disappearance pharmacokinetics, pharmacodynamics and general tolerance of i.v. timolol were compared in 12 healthy volunteers and 10 patients with a definite or proven acute myocardial infarction. The drug was administered to the patients immediately on arrival at the hospital after a median delay time of 4 h. Tolerance to the injections was good in both volunteers and patients. The study revealed disappearance pharmacokinetics that were similar in volunteers and patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01061376
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  • 162
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of metipranolol in normal man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 293-301 
    Details
    ISSN: 1432-1041
    Schlagwort(e): metipranolol ; deacetyl metipranolol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic parameters of deacetyl metipranolol were determined after i.v. infusion of increasing doses (6–25 mg) in 17 normal volunteers. In a second cross-over trial, deacetyl metipranolol 10 and 20 mg were infused in a further 10 subjects, and in a third trial another 20 volunteers received metipranolol 40 mg orally. Metipranolol is very rapidly and completely deacetylated in man, so all pharmacokinetic data refer to deacetyl metipranolol, which was assayed by gas chromatography-mass spectrometry. The pharmacokinetic analysis was performed using a recently developed model, using a volume of distribution which is variable with time. The following data were obtained after oral administration: (mean values); lag-time 7.3 min; tmax 50 min, invasion half-life 6.3 min; elimination half-life 3 h; urinary excretion of unchanged drug approximately 4% of the dose. The experiments with infusion of increasing doses, as well as the cross-over study with 10 and 20 mg i.v., showed dose-linearity of the kinetics. The respective mean half-lives of elimination were 2.6, 2.9 and 2.8 h. The mean total, renal and extra-renal clearances amounted to 1237 ml/min, 149 ml/min and 1068 ml/min, respectively. The distribution coefficient was 3.5 l/kg, and protein binding amounted to 70% within the range of therapeutic concentrations. Absolute bioavailability was found to be approximately 50% by several different evaluation procedures. Thus, the pharmacokinetic profile of metipranolol shares features of both the lipophilic and the hydrophilic groups of β-blocking agents.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637616
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  • 163
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of bendroflumethiazide alone and in combination with propranolol and hydralazine (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 315-323 
    Details
    ISSN: 1432-1041
    Schlagwort(e): bendroflumethiazide ; propranolol ; hydralazine ; pharmacokinetics ; thin-layer chromatography ; fluorimetry ; fixed combination product
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Bendroflumethiazide (Bft) was administered to 6 healthy subjects at 3 different dose levels (2.5, 5 and 10 mg) in a cross-over design, either as capsules (2.5 mg) or as tablets (5 mg). Its pharmacokinetics were evaluated then and following administration of a fixed combination of Bft with propranolol and hydralazine to a further 7 volunteers. Plasma and urinary concentrations of Bft were determined by a new fluorimetric — thin-layer chromotography procedure. Peak plasma levels occurred after 2–3 h and averaged 15, 27 and 45 µg/l in the three dose groups. Areas under the plasma concentration — time curves (AUC0→12), which were 75, 147 and 250 µg l−1 h respectively, and cumulative urinary recovery (20%) were independent of the dose administered and the type of formulation. Thus Bft kinetics proved to be linear within the dose range evaluated. The plasma clearance was calculated to be 505 ml/min, renal clearance 108 ml/min and nonrenal clearance 396 ml/min. Bioavailability of Bft was not altered following administration of the fixed combination. The amount of propranolol found in the circulation did not change, whereas that of hydralazine (determined as apparent hydralazine) increased by 59% when the fixed combination was administered.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637620
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  • 164
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and biotransformation of the new benzodiazepine, lormetazepam, in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 421-425 
    Details
    ISSN: 1432-1041
    Schlagwort(e): benzodiazepine ; lormetazepam ; lormetazepam glucuronide ; transfer to milk ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The concentrations of lormetazepam and its glucuronide in plasma and milk were determined during administration of 10 daily doses of lormetazepam 2 mg (2 tablets of NOCTAMID® - 1) to five mothers delivered by Caesarian section. Their babies were breast-fed throughout the study, and the plasma levels of lormetazepam and its glucuronide were determined three times in the babies. At 12 and 24h after administration, the plasma level of lormetazepam was about 3.5 ng/ml and 1.8 ng/ml in mothers, and below 0.09 ng/ml in the children. In milk the lormetazepam concentration was below 0.2 ng/ml. The plasma level of glucuronide varied between 24 ng/ml at 12h and 11 ng/ml 24h after administration. Almost no accumulation of unchanged lormetazepam was observed (factor: 1.3). The ratio of the levels of lormetazepam in milk and plasma was estimated to be below 0.06, and for the glucuronide the ratio was 0.04. The quantity of free and conjugated active ingredient transferred to the children via breast milk was calculated to be at most 100 ng/kg, corresponding to 0.35% of the maternal dose, which is regarded as tolerable.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542330
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  • 165
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of gentamicin in malnourrished infants (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 499-504 
    Details
    ISSN: 1432-1041
    Schlagwort(e): gentamicin ; malnutrition ; pharmacokinetics ; infant
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of gentamicin was investigated in normal and malnourished infants aged 4–10 months. Neither mean “elimination” nor “distribution half life” show any difference, but the volume of distribution was higher in malnourished babies, probably due to their larger total body water.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542045
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  • 166
    Digitale Medien
    Digitale Medien
    Metabolism of pindolol in patients with renal failure (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 423-428 
    Details
    ISSN: 1432-1041
    Schlagwort(e): pindolol ; renal failure ; metabolism ; pharmacokinetics ; 14C-pindolol ; blood metabolites ; urinary metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Increased metabolism of pindolol in renal impairment has previously been suggested by pharmacokinetic calculations. The present study was a pharmacokinetic and metabolic investigation in 7 patients with severe renal impairment (endogeneous creatinine clearance below 5 ml/min). All the patients received pindolol 5 mg t.d.s. 5 days. On the sixth day, after an overnight fast, 14C-pindolol 5 mg was given orally as a solution to drink. Blood samples were taken for up to 72 h and urine was collected at intervals up to 96 h for measurement of unchanged pindolol by a fluorimetric method and total radioactivity by liquid scintillation counting. Metabolites in blood and urine were analysed after separation by HPLC. It was found that the plasma levels following a single dose of 14C-pindolol were similar to those observed in healthy volunteers, but the elimination half-life was slightly increased up to 11.5 h. The observed steady state plasma concentrations of pindolol were twice as high but they are still in the therapeutic range of 10 to 100 ng/ml. Therefore, the dose of pindolol could have been reduced by a factor 2, but the reduction was not essential. No active metabolite of pindolol was found in plasma or urine, but elimination of the metabolites was decreased. The elimination half-life following multiple doses was prolonged compared to normal and it was quite comparable to that found for the pharmacodynamic half-life in renal patients. The discrepancy between the present findings and the previous results for metabolism and pharmacodynamic half-life was probably due to the sensitivity of the fluorimetric assay of pindolol.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542547
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  • 167
    Digitale Medien
    Digitale Medien
    Modification in the pharmacokinetics of amikacin during development (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 155-160 
    Details
    ISSN: 1432-1041
    Schlagwort(e): amikacin ; pharmacokinetics ; development ; neonate ; infant ; child
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition kinetics of a single i.v. dose of amikacin was studied in 6 neonates (6–25 days old), 10 infants (4–18 months) and 8 young children (3–11 years). There was a progressive change in the distribution and elimination kinetics during development. The distribution coefficient of the antibiotic averaged of 0.429, 0.320 and 0.210 l/kg in the newborns, infants and young children, respectively and serum half-life (t1/2 β) in these three groups averaged 2.812, 1.803 and 1.196 h, respectively. Significant differences in certain pharmacokinetic parameters were found between the values in paediatric patients and in adults receiving the same dose. A linear relationship was established between the distribution volume of the antibiotic and the weight of the patients, as defined by the following equation: $${\text{Vd}}_{{\text{ss}}} \left( 1 \right) = 0.976 + 1.140 \cdot {\text{TBW}}\left( {{\text{kg}}} \right);r = 0.954$$ The results suggest that a regimen of very frequent administrations should be employed in infants and young children in order to maintain a therapeutic level throughout treatment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00545971
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  • 168
    Digitale Medien
    Digitale Medien
    Clinical pharmacokinetics of high dose mebendazole in patients treated for cystic hydatid disease (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 161-169 
    Details
    ISSN: 1432-1041
    Schlagwort(e): mebendazole ; hydatid disease ; Echinococcus granulosus ; hepatic disease ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentrations of mebendazole and its metabolites have been monitored in twelve patients after receiving a 10 mg/kg dose for cystic hydatid disease. The mebendazole plasma concentration-time profiles differed considerably between patients; elimination half-lives ranged from 2.8–9.0 h, time to peak plasma concentration after dosing ranged from 1.5–7.25 h and peak plasma concentrations ranged from 17.5 to 500 ng/ml. The mean peak plasma concentration of mebendazole after an initial dose (69.5 ng/ml) was lower than found in patients during chronic therapy (137.4 ng/ml). The plasma AUCTs for the major metabolites of mebendazole (methyl 5-(α-hydroxybenzyl)-2-benzimidazole carbamate and 2-amino-5 benzoylbenzimidazole) were about five times the plasma AUCT found for mebendazole in patients on chronic therapy. It is suggested that the slower clearance of these polar metabolites relative to mebendazole results from enterohepatic recycling. Since mebendazole is also highly plasma protein bound, caution should be observed in administering mebendazole to patients with liver disease. Concentrations of mebendazole found in the tissue and cyst material collected from two patients during surgery ranged from 59.5 to 206.6 ng/g wet weight.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542462
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  • 169
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of parenteral and oral melperone in man (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 173-176 
    Details
    ISSN: 1432-1041
    Schlagwort(e): melperone ; neuroleptic drug ; dose dependent kinetics ; i.m. injection ; i.v. injection ; pharmacokinetics ; oral application
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of melperone (Buronil®, Ferrosan, Sweden) was studied after administration of various parenteral and oral doses to man. After parenteral administration, the data could be fitted to a two-compartment model, but after oral dosing the distribution phase could not be separated from the elimination phase, and so an one-compartment model gave the best fit. The half-lives were about 3–4 h, except after intramuscular injection, when the half-life was about 6 h. The bioavailability of oral doses was about 60% of the intravenous injection. After the highest oral dose of 100 mg, the pharmacokinetics, expressed as AUC or Cmax, showed non-linearity, possibly due to saturation of the hepatic elimination system.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00545974
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  • 170
    Digitale Medien
    Digitale Medien
    Distribution of oral ketoconazole to vaginal tissue (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 331-333 
    Details
    ISSN: 1432-1041
    Schlagwort(e): ketoconazole ; vaginal candidosis ; oral antimycotic ; distribution ; pharmacokinetics ; vaginal tissue concentrations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma samples and biopsies of vaginal tissue were obtained from 23 healthy women undergoing operative sterilization, 1 to 6 h after a single oral dose of ketoconazole 200 mg. Drug concentrations in plasma and tissue, were measured by a specific gas chromatographic method. The vaginal tissue concentration averaged 2.4 times less than the corresponding plasma levels. Equilibrium between tissue, and plasma was established within 1 h after dosing, when vaginal tissue levels exceeded 1 µg/g. Ketoconazole concentrations decayed monoexponentially over the time interval studied (1–6 h), with the similar half-lives of 1.2 and 1.4 h in plasma and tissue, respectively. Following an oral 200 mg dose, a tissue concentration not less than 0.01 µg/ml was maintained over a 12 h period. This concentration has been shown to prevent outgrowth of the invasive (pseudo) mycelial form ofCandida albicans. Hence, a b.i.d. or t.i.d. dosage schedule of ketoconazole in vaginal candidosis would give continuously effective levels at the site of infection. Ketoconazole concentrations in vaginal fluid are thought to be much higher than in the tissue because of ion-trapping. The present data may explain the efficacy of oral ketoconazole in the treatment of vaginal candidosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613615
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  • 171
    Digitale Medien
    Digitale Medien
    Kinetics of furosemide in children with chronic renal failure undergoing regular haemodialysis (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 303-306 
    Details
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; renal failure ; haemodialysis ; pharmacokinetics ; children ; dosage schedule
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Furosemide was measured by gas-liquid chromatography in blood and dialysis fluid from 7 children with chronic renal failure, undergoing regular haemodialysis. It was administered chronically, in two or three daily doses (4.2–9.4 mg/kg). Two children received 1 mg/kg intravenously for determination of the pharmacokinetics. The half-life was longer than in adults and in anephric patients on haemodialysis. Systemic and renal clearance were also much lower. Plasma protein binding in 2 out of 6 cases was reduced as campared to normal adults. The data do not suggest any need to modify the present dosage schedule despite the 4–5 fold increase in the half-life of furosemide. The contribution of haemodialysis to drug clearance was minimal, and accounted for less than 10% of the total clearance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637617
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  • 172
    Digitale Medien
    Digitale Medien
    The pharmacokinetics of diclofenac sodium in patients with active rheumatoid disease (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 331-334 
    Details
    ISSN: 1432-1041
    Schlagwort(e): diclofenac sodium ; rheumatoid disease ; healthy subjects ; serum albumin ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pharmacokinetic data for diclofenac sodium has been well established in healthy volunteers, whereas in patients with rheumatoid arthritis very little information is available in the literature. A single oral dose of enteric-coated diclofenac sodium was given to 10 patients with active rheumatoid disease, adopting the same procedures used for a group of 10 healthy volunteers in whom pharmacokinetic data was already available. Plasma specimens were collected over a period of 8h following administration and concentrations of diclofenac determined by GLC. Resulting plasma concentration curves were similar to those obtained in the healthy subjects in that areas under curves and terminal half-lives were comparable. However, peak concentrations of diclofenac were significantly reduced in the rheumatoid patients. The lower peak concentrations were correlated with the lower serum albumin levels in the patients which are associated with active rheumatoid disease.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637622
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  • 173
    Digitale Medien
    Digitale Medien
    Pharmacokinetic aspects of caffeine in premature infants with apnoea (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 47-52 
    Details
    ISSN: 1432-1041
    Schlagwort(e): apnoea ; caffeine ; premature infants ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of caffeine was examined in 13 premature infants (gestational age 25–34 weeks, birth weight 920–2060 g, postnatal age 1–42 days) who received the drug for treatment of opnoea. Caffeine (1% aqueous solution) was given i.v. in single doses; guided by the clinical response infants received between one and seven (mean 2.6) doses of 15 mg/kg. Mean (± SE; range) Clb was extremely slow − 8.5 ml/kg/h (±0.4; 5.8–12.2), t1/2 was prolonged − 65.0 h (±3.7; 48.2–87.5 h) and Vd was 0.781/kg (±0.04; 0.47–1.01). No significant correlation was found between Clb, t1/2 and postnatal age in the whole group or in individual infants. Effective plasma concentrations varied over a wide range (12–36 µg/ml) and overlapped with subtherapeutic concentrations (⩽24 µg/ml). Single doses of 15 mg/kg i.v. or p.o. prevented apnoea in most cases, if necessary followed by additional doses. Monitoring the blood level of caffeine in infants receiving frequent repeated doses is necessary to prevent toxicity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606424
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  • 174
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of chlorpheniramine after intravenous and oral administration in normal adults (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 359-365 
    Details
    ISSN: 1432-1041
    Schlagwort(e): chlorpheniramine ; pharmacokinetics ; oral absorption ; half-life ; bioavailability ; volume of distribution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma and urinary levels of chlorpheniramine (CPM) and its 2 demethylated metabolites were measured by HPLC after i.v. and oral dosing. In 5 mg (maleate) i.v. bolus studies in 2 subjects, plasma CPM levels were fitted to triexponential equations with terminal half-lives (t 1/2) of 23 and 22 h and area of 3.6 and 3.21/kg, respectively. Intravenous data predicted hepatic blood extraction ratios for the 2 subjects to be 0.06 and 0.07, respectively. Absolute bioavailability from oral solution (10 mg) was 59 and 34%, and from tablets (8 mg) 44 and 25%, respectively, indicating extensive gut first-pass metabolism. Mean t 1/2 from 7 oral fasting studies in 5 subjects was 28 h (19–43 h). Mean absorption lag time was 0.7 h (0.4–1.3 h), and mean peak time was 2.8 h (2–4 h). In 2 subjects, 6 mg solutions were given every 12 h for 9 doses; good correlation between single and multiple dose kinetics was found. Significant accumulation was demonstrated in simulation studies with frequent daily dosing. Estimated accumulation ratios vary from 4.1 to 9.4 (mean 6.5). The t 1/2 from urinary data (collected for 12 days) was consistent with plasma data. The above results suggest the need to reexamine the current practice of frequent daily dosing and the use of sustained or controlled release dosage forms of this drug. The possible cause of reduced plasma clearance of CPM in renal patients is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548406
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  • 175
    Digitale Medien
    Digitale Medien
    The clinical pharmacology of tolmesoxide (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 93-97 
    Details
    ISSN: 1432-1041
    Schlagwort(e): tolmesoxide ; vasodilator ; hypertension ; pharmacokinetics ; haemodynamics ; plasma renin activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The haemodynamic response and pharmacokinetics of single dose oral tolmesoxide were studied at various dose levels in 4 patients with severe hypertension. There was a reproducible fall in mean arterial pressure from baseline of 24.2% and a rise in heart rate of 37.6% following administration of tolmesoxide. The onset of antihypertensive action occurred within 1 h, with a peak effect at 3 h after dosing. The mean duration of action was up to 12.0 h. Tolmesoxide had a mean half-life of 3.0 h. It was rapidly absorbed with a mean peak plasma level occurring at 1.0 h. Plasma levels correlated well with the doses administered. Side-effects included mild nausea, facial flushing and postural symptoms.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00545961
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  • 176
    Digitale Medien
    Digitale Medien
    Variability of beta-blocker pharmacokinetics in young volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 37-42 
    Details
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; propranolol ; oxprenolol ; pharmacokinetics ; acetubolol ; diacetolol ; oral contraceptive
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations of metoprolol, propranolol oxprenolol, acebutolol and its metabolite diacetolol were measured after single oral doses in young healthy volunteers. In order to assess the inter-and intra-subject variability the following pharmacokinetic parameters were compared: AUC o 24 , Cmax, tmax and t1/2. The smallest variation in inter-subject variability was seen with oxprenolol and acebutolol: intrasubject variability was more uniform. Female volunteers taking an oral contraceptive generally had higher AUC o 24 and Cmax values than those not. This finding reached statistical significance only for metoprolol AUC o 24 .
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01061375
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  • 177
    Digitale Medien
    Digitale Medien
    Clinical pharmacokinetics of verapamil in patients with atrial fibrillation (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 49-57 
    Details
    ISSN: 1432-1041
    Schlagwort(e): verapamil ; norverpamil ; pharmacokinetics ; atrial fibrillation ; oral administration ; i.v. administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic parameters and oral bioavailability of the antiarrhythmic drug verapamil were determined in six patients with atrial fibrillation. Plasma samples were taken following i.v. injection of verapamil 10 mg (Isoptin® 2 ml), and oral verapamil 80 mg (Isoptin® 2 tablets of 40 mg). Verapamil and its N-demethylated metabolite, norverapamil, were analyzed to 1 ng/ml plasma by gas chromatography-mass spectrometry using deuterated standards. Following intravenous injection, the disposition of verapamil followed a biexponential pattern with a fast distribution phase and a slower elimination phase (t1/2β=5.79 h), corresponding to a plasma clearance of 0.26 1/kg/h. After oral administration, only an elimination phase was evident, with the same elimination rate (t1/2β=5.53 h). The oral bioavailability was 10.5%±7.5%. The norverapamil formed after i.v. and oral administration of verapamil had plasma half-lives of 5.86 h and 6.77 h, respectively. The elimination of verapamil in patients with atrial fibrillation was decreased compared to that in healthy young volunteers and the oral bioavailability was lower. Very good correlation between the percentage reduction in heart rate and the log plasma concentration of verapamil was found in every patient during the elimination phase, irrespective of the route of administration. There was also a high correlation when the plasma concentration — effect data from all the patients were pooled (r=0.59,n=71;p〈0.0005).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01061377
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  • 178
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of theophylline in infants with bronchiolitis (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 123-127 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; bronchiolitis ; infants ; pharmacokinetics ; single dose ; multiple doses ; HPLC
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Theophylline pharmacokinetics were studied in 12 infants (age 3 weeks–6.5 months) with bronchiolitis. 9 of the 12 patients received a single dose of aminophylline (5.0–8.5 mg/kg) whereas the remainder were at steady-state receiving multiple doses (2.5–5.0 mg/kg) of aminophylline. The dose was administered IV over 0.5–1.0 h. An HPLC method was used to measure theophylline concentrations in serum and urine. Peak serum concentrations of theophylline measured by HPLC ranged from 8.48–21.6 µg/ml. Total, renal and nonrenal clearance of theophylline ranged from 4.66 to 19.25, 1.07 to 5.76 and 3.59 to 16.83 ml/min/m2, respectively. Mean apparent volume of distribution and elimination half-life were 8.75 l/m2 and 11.38 h, respectively. Although no significant correlation was observed between age and theophylline kinetic parameters, clearance appeared to increase and half-life decrease with age. Our patients had a substantially lower clearance and longer half-life as compared to published data in children 〉1 year of age. A five-fold variation in theophylline clearance demonstrates the need for monitoring theophylline serum concentration to minimize the risk of potential toxicity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00545965
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  • 179
    Digitale Medien
    Digitale Medien
    Effect of chronic oral contraceptive steroids on theophylline disposition (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 129-134 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; ethinylestradiol ; oral contraceptives ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of chronic oral contraceptive (OC) usage on the disposition of theophylline was examined. Aminophylline solution (4 mg/kg) was given orally to 8 healthy female non-OC users and to 8 healthy women who were chronic (〉6 months) OC users. The OC user group had a significantly lower total plasma clearance of theophylline than women not using OC (35.1±5.6 vs. 53.1±14.5 ml/h/kg). The t1/2 was also significantly prolonged in the OC group (9.79±1.43 vs. 7.34±1.75 h) while the volume of distribution was similar between the 2 groups. The serum ethinylestradiol (EE) concentrations after oral OC administration were measured simultaneously. The apparent clearance of EE was about 30% lower in the OC users. A significant positive correlation was found between the apparent clearance of EE and the plasma clearance of theophylline. The effects of OC are predominantly due to chronic use with decreased elimination of both theophylline and EE.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00545966
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  • 180
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of ticarcillin in man (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 167-172 
    Details
    ISSN: 1432-1041
    Schlagwort(e): ticarcillin ; probenecid ; excretion ; pharmacokinetics ; automated chemical assay method
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The excretion of radioactivity has been investigated in 3 healthy volunteers following rapid intravenous administration of 5 g of [35S]-ticarcillin. The radioactive dose was rapidly and completely excreted, since within 4 days 98.5% was recovered, 95% in the urine and 3.5% in faeces. All the urine radioactivity was accounted for as ticarcillin and its penicilloic acid. Plasma and urine samples collected from the volunteers at frequent intervals during the first 6 h of the experiment were assayed for penicillin by an automated chemical method and also for radioactivity. The results obtained by the chemical autoanalyser method were in excellent agreement with the plasma levels of radioactivity. From the data it was possible to calculate the renal clearance of the penicillin, a mean value of 104 ml/min was observed in the 3 volunteers. A further three volunteers were dosed intravenously with a 5 g bolus of non-radiolabelled ticarcillin in a cross-over study with and without predosing with probenecid. Serum samples were analysed by the chemical method for penicillin and the data subjected to pharmacokinetic analysis using a two compartment open model. The results indicate a shift of the distribution equilibrium of ticarcillin from the serum into the peripheral compartment after predosing with probenecid. Furthermore, the mean half-life of ticarcillin in the serum of the three volunteers was significantly increased from 1.3 h to 2.1 h by predosing with probenecid.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00545973
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  • 181
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of oral dipyridamole (Persantine®) and its effect on platelet adenosine uptake in man (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 229-234 
    Details
    ISSN: 1432-1041
    Schlagwort(e): dipyridamole ; platelets ; plasma levels ; pharmacokinetics ; adenosine uptake
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Two preparations of dipyridamole have been studied by oral administration to 11 normal volunteers. The plasma levels of dipyridamole and its glucuronide were determined simultaneously by high performance liquid chromatography. The instant form (I.F., 100 mg) was administered four times daily and the slow release preparation (SRP, 200 mg) twice daily, for 3 days. Multiple blood samples were collected on Days 1–4 to provide plasma for assay, and simulteneously, platelet rich plasma was prepared for ex vivo study of the effect of dipyridamole on platelet uptake of adenosine. The pharmacokinetics of absorption and distribution of dipyridamole were described using a two compartment model with lag time and prolonged absorption. Strong inhibition of the platelet adenosine uptake was observed at therapeutic plasma levels. The inhibition of platelet adenosine uptake may be related to some of the pharmacological properties of dipyridamole.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00547559
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  • 182
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and tolerance of slow-release indomethacin tablets in rheumatoid arthritis (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 349-351 
    Details
    ISSN: 1432-1041
    Schlagwort(e): indomethazine ; rheumatoid arthritis ; pharmacokinetics ; tolerance ; side effects ; slow-release tablets
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics, efficacy and tolerance of a new formulation of slow-release indomethacin tablet were compared with those of a conventional indomethacin capsule in 30 patients with rheumatoid arthritis. The slow-release tablet was absorbed more slowly than the capsule (tmax 3.7 h and 〈 2 h, respectively) and produced more even serum drug levels in 10 subjects. Side-effects, especially dizziness and diarrhoea, were less frequent after the slow-release tablet than during the capsule period.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613619
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  • 183
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of3H-phenylephrine in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 335-341 
    Details
    ISSN: 1432-1041
    Schlagwort(e): phenylephrine ; pharmacokinetics ; bioavailability ; first-pass metabolism ; phenolic conjugates ; m-hydroxymandelic acid ; intravenous ; oral
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary 7-3H-phenylephrine was given to 15 volunteers by a short-infusionn=4) or p.o. (10 volunteers, 1 patient with porto-caval anastomosis). Analysis of serum for free3H-phenylephrine and fractionation of urinary radioactivity was performed by ion-exchange and thin-layer chromatography. As almost the same3H-activity was excreted in urine after i.v. and p.o. administration, 86% and 80% of the dose respectively, complete enteral absorption can be assumed. A considerable difference was seen in the fraction of free phenylephrine, i.v. 16% of the dose versus p.o. 2.6%, which suggested reduced bioavailability. This was confirmed by comparison of the areas under the serum curve, which showed a bioavailability factor of 0.38. The result for the patient with porto-caval anastomosis was comparable to that in the normal volunteers. The biological half-life of 2 to 3h was comparable to that of structurally related amines, as were the total clearance of 2 1/h, and the volume of distribution of 340l. Metabolism to phenolic conjugates mainly after oral ingestion, and tom-hydroxymandelic acid after i.v. injection, again demonstrated thatm-hydroxylated amines are predominantly conjugated during the “first-pass” metabolism.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637623
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  • 184
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of furosemide in patients with hepatic cirrhosis (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 315-320 
    Details
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; cirrhotic patients ; ascitic fluid ; diuretic effect ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of furosemide was studied in 7 patients with diagnosed liver cirrhosis and in 7 healthy subjects. Furosemide in plasma and ascitic fluid was analyzed spectrofluorometrically. After a single intravenous dose, the cirrhotic patients showed lower initial plasma concentrations of furosemide because of the larger volume of distribution. The mean half-life in cirrhotic patients was significantly greater than in healthy volunteers. The longer half-life was associated with a reduction in the serum clearance of furosemide. Ascitic fluid volume in the patients ranged from 4.6 to 7.71. There was no significant amount of furosemide in the fluid. The diuretic interchange between this fluid and plasma was slow, as peak concentrations ranged from 0.3 to 0.5 µg/ml within 3 to 5 h after bolus administration of furosemide. Diuresis and urinary sodium excretion, 5 h after furosemide injection, were similar in both groups; larger potassium excretion was found in the cirrhotic patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548399
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  • 185
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of cimetidine and its sulphoxide metabolite during haemodialysis (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 325-330 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; renal failure ; cimetidine sulphoxide ; pharmacokinetics ; haemodialysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A single intravenous dose of cimetidine 200mg was administered to 6 patients with severe chronic renal failure one hour prior to haemodialysis. The plasma concentrations of cimetidine and its sulphoxide metabolite at the start of haemodialysis were 2.74±0.12 and 0.76±0.08 µg/ml, and after dialysis for 4h 1.08±0.10 and 0.51±0.08 µg/ml, respectively (mean ± SE). The average haemodialysis clearance (ClHDa) of cimetidine during dialysis was 46–92ml/min at a dialysate flow rate of 320ml/min and blood flow rates in the 6 patients between 160–240ml/min. The mean ClHDa of the sulphoxide metabolite was 44% higher than that of cimetidine, and ranged between 49–148ml/min. During haemodialysis the mean plasma elimination half-life (t1/2) of cimetidine was 3.24h (range 2.08–5.08) and of the sulphoxide metabolite 9.49h (range 4.70–14.39). There was a significant relationship between the elimination rate constant (β) and ClHDa of the sulphoxide metabolite (p〈0.01), but no such relationship was found between β and ClHDa of cimetidine. However, there was a tendency to a relationship between β of cimetidine and the capacity to metabolise the drug, expressed as the ratio between the plasma concentrations of the sulphoxide metabolite and cimetidine after dialysis for 4h. These ratios ranged between 0.23–0.76, and the lowest ratio was seen in the patient with the lowest β value of cimetidine. Thus, the large variations in the plained by differences in their capacity to metabolise the drug. The mean total amount of cimetidine eliminated during dialysis was 27.3mg (range 17.9–31.8), which was 9.0–15.9% of the given dose. Between 12.2–21.2mg (mean 15.3) of the sulphoxide metabolite was eliminated in the dialysate. Major adjustment of the dose of cimetidine on days of dialysis is not necessary.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637621
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  • 186
    Digitale Medien
    Digitale Medien
    Distribution of lithium elimination rates in a selected population of psychiatric patients (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 351-354 
    Details
    ISSN: 1432-1041
    Schlagwort(e): lithium ; plasma level decay curve ; elimination ; pharmacokinetics ; psychiatric patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Chronic treatment with conventional lithium carbonate was interrupted in a selected group of 40 psychiatric patients of mixed sex and race. All patients had normal renal function. Serum samples were taken 12, 24, 36 and 48 h after the last dose and lithium was assayed by atomic absorption spectrophotometry. Decay rates calculated for the 12–24 h and 36–48 h periods yielded different values. This was ascribed to the presence of an incomplete redistribution phase during the earlier period. The distribution of elimination rates determined during the later period gave a more symmetrical spread and approximated a normal distribution. The mode, median, mean and standard deviation of the lithium elimination half-lives were 12.5, 14, 18.2 and 7.3 h and 22.5, 24.5, 29.8 and 10.1 h for the two periods, respectively. The results contrast sharply with another report of the distribution spread of elimination half-lives in a much larger sample. The current values have implications for dosage prediction, serum level monitoring and dosage formulation, especially sustained-release preparations. The evidence was against the possibility that some individuals ‘retain’ lithium.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637625
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  • 187
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of propranolol and sotalol in hyperthyroidism (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 373-377 
    Details
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; sotalol ; thyrotoxicosis ; bioavailability ; serum tri-iodothyronine ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The elimination and bioavailability of two beta-blocking agents, propranolol and sotalol, were studied in 10 thyrotoxic patients, both before and after treatment with iodine-131. Each subject received in random order propranolol 160 mg and sotalol 160mg as single oral doses both while hyperthyroid and after euthyroidism had been achieved. The pharmacokinetics of sotalol was not affected by hyperthyroidism, whereas serum propranolol concentrations were significantly lower during hyperthyroidism than in the euthyroid state. During hyperthyroidism, the bioavailability of propranolol was significantly reduced (p〈0.05) and its clearance was increased (p〈0.005), whereas there was no difference in its serum t1/2. This indicates that the bioavailability of propranolol in hyperthyroidism is reduced by a mechanism which may depend on increased first-pass metabolism in the liver, or on an increased distribution volume of the drug. Both propranolol and sotalol caused a slight decrease in serum tri-iodothyronine concentration. As the effects of beta-blocking agents on the symptoms of hyperthyroidism are correlated with the serum concentration of the drugs, sotalol, with its long half-life and unaltered elimination in hyperthyroidism, has certain advantages over propranolol in the treatment of thyrotoxicosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542321
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  • 188
    Digitale Medien
    Digitale Medien
    Studies of the different metabolic pathways of antipyrine in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 433-441 
    Details
    ISSN: 1432-1041
    Schlagwort(e): antipyrine ; antipyrine metabolites ; drug metabolism ; route of administration ; healthy volunteers ; urinary excretion ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of antipyrine in plasma and saliva, and urinary excretion of its major metabolites, were studied following i.v. and oral administration of antipyrine 500 mg to 6 healthy volunteers. Data from both plasma and saliva showed that the oral bioavailability of antipyrine given as an aqueous solution was complete. The saliva/plasma concentration ratio was constant with time from about 3 h onwards, with a mean value of 0.87 after oral and 0.91 after i.v. administration. It is concluded that the pharmacokinetic parameters of antipyrine can be satisfactorily established on the basis of salivary data, although the volume of distribution and clearance values are then slightly too high. After i.v. administration, 3.8±1.9% of the dose was excreted in urine as unchanged antipyrine in 48h, 24.9±6.3% as 4-hydroxyantipyrine, 16.5±3.2% as norantipyrine, 13.0±2.2% as 3-hydroxymethyl-antipyrine and 5.8±1.0% as 3-carboxy-antipyrine. No significant differences were observed following oral administration. The half-lives calculated from the linear part of the urinary excretion rate curves of the metabolites were about the same for oral and i.v. administration, and were of the same order of magnitude as the elimination half-life of parent drug in plasma and saliva. It is important for determination of the ultimate metabolite ratio that urine is collected for at least 36h, because there is a delay in the excretion of 3-hydroxymethyl-antipyrine in urine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542332
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  • 189
    Digitale Medien
    Digitale Medien
    Relationship between the plasma concentration of clomipramine and desmethylclomipramine in depressive patients and the clinical response (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 15-20 
    Details
    ISSN: 1432-1041
    Schlagwort(e): clomipramine ; desmethylclomipramine ; depressive syndrome ; plasma level ; pharmacokinetics ; clinical response ; benzodiazepines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Thirty one in-patients suffering from depression were treated orally with clomipramine (Cl) at various dosage, for 28 days, after a “wash-out” period of three days. In 17 patients receiving 75 mg per day of Cl, steady state plasma levels of Cl were reached at Day 14, and steady state plasma levels of its active metabolite, desmethylclomipramine (DMCl), were reached at Day 21. In contrast, in 7 other patients receiving a dosage increasing to 150 mg per day at Day 7, mean plasma levels of Cl and DMCl continued to rise during the entire treatment period. At the steady state, a correlation was found between Cl dosage expressed as mg kg body weight and the plasma concentration of Cl and DMCl. Factors such as tobacco and alcohol consumption seem to modify the Cl/DMCl ratio. A comparison of clinical response with plasma levels of Cl, DMCl and Cl + DMCl showed a significant negative linear correlation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606419
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  • 190
    Digitale Medien
    Digitale Medien
    Kinetics of allopurinol after single intravenous and oral doses (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 77-84 
    Details
    ISSN: 1432-1041
    Schlagwort(e): allopurinol ; oxipurinol ; benzbromarone ; hydrochlorothiazide ; pharmacokinetics ; bioavailability ; interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary An high-pressure liquid chromatographic method was used to measure allopurinol and oxipurinol in plasma and urine in 6 healthy volunteers after a single intravenous or oral dose of allopurinol. The influence of coadministrated benzbromarone and hydrochlorothiazide on the pharmacokinetics of allopurinol and oxipurinol was also investigated. After intravenous injection of allopurinol 300 mg the plasma disappearance was biexponential, with a mean distribution half-life of 2.32±1.08 min $$(\bar x \pm SD)$$ and an elimination half-life of 47.8±10.6 min. The total clearance of allopurinol was 11.37±2.70 ml/min/kg, whereas its renal clearance was only 1.73±0.79 ml/min/kg. Oxipurinol disappeared monoexponentially from plasma ith a mean half-life of 12.2±2.6 h. Its renal clearance was 0.42±0.091 ml/min/kg. After oral administration of allopurinol 300 mg the peak plasma concentration of 2.1±0.6 µg/ml (1.5×10−5 M) was reached within 30 to 120 min. The peak level of oxipurinol of 5.8±1.5 µg/ml (3.8×10−5 M) was found within 2 to 5 h after intravenous and oral allopurinol. The bioavailability of oral allopurinol computed from plasma data was 90.4±8.7%. The total recovery from urine was 77% (allopurinol 8%, oxipurinol 69%) after oral and 88% after i.v. administration. It was concluded that about 10% of the oral dose was not absorbed and that 12% was eliminated by an unknown mechanism, presumably as riboside. The pharmacokinetics of allopurinol and oxipurinol were not significantly influenced by coadministration of benzbromarone or hydrochlorothiazide.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606429
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  • 191
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of methadone during maintenance treatment: Adaptive changes during the induction phase (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 343-349 
    Details
    ISSN: 1432-1041
    Schlagwort(e): methadone ; opiate addicts ; pharmacokinetics ; single and multiple doses ; stable isotope technology ; methadone maintenance therapy ; deuterium technique
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Deuterated methadone (M-d30) and GC-MS were used to study the pharmacokinetics of methadone (M) during the induction stage of methadone maintenance treatment (MMT). A pulse dose of M-d3 was given on Days 1 and 25 of two dosage regimens, one with a continuous 30 mg dose (n=6), and the other with 30 mg for 10 days, followed by 60 mg as the maintenance dose (n=6). Plasma and urinary levels of M and M-d3 were measured throughout and plasma half-lives, oral bioavailabilities and volumes of distribution were calculated from the data of Days 1–2 and 24–26. The oral bioavailability of a methadone solution was found to be between 81 and 95%; elimination half-life in the β-phase varied between 19 and 58 h; the volume of distribution was 4.1±0.65 l/kg; and total body clearance of M was 54–195 ml/min and its renal clearance 3.4–34 ml/min. A consistent finding was a lower urinary pH and increased renal clearance during the first days of MMT as compared with after one month. In 4/12 of the patients dispositional tolerance was developed to methadone during the first month of treatment. The shorter elimination half-lives in those patients probably caused unacceptably high fluctuation in the body content of M during the 24 h dosage interval, and may have interfered therefore, with its therapeutic effectiveness
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548404
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  • 192
    Digitale Medien
    Digitale Medien
    Pharmacokinetic and pharmacodynamic studies of tienilic acid in healthy volunteers (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 515-521 
    Details
    ISSN: 1432-1041
    Schlagwort(e): tienilic acid ; uricosuria ; pharmacokinetics ; pharmacodynamics ; uric acid ; diuretic ; plasma level assay
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A simple and reliable HPLC method for the determination of tienilic acid ((TA) Selacryn®, Selcryn®, Diflurex®, Ticrynafen®) and its alcoholic metabolite in plasma and urine has been developed. In 8 healthy adult volunteers the plasma and urinary levels of tienilic acid and its alcoholic metabolite, and plasma and urinary levels of sodium, creatinine and uric acid were measured after oral administration of tienilic acid 250 mg. The pharmacokinetic parameters found differed only slightly from those reported in the literature, as there was faster absorption and a shorter half-life. TA is probably excreted by a saturable renal tubular transport mechanism. The pharmacodynamic effects of tienilic acid developed quickly, the uricosuric effect being very impressive and the natriuretic effect moderate. These effects disappeared in about 8 h. An inverse relationship was found between the starting plasma uric acid level in an individual and the maximal uric acid clearance — the higher the plasma uric acid level, the lower was the maximum effect. Plasma tienilic acid level and natriuretic effect were correlative within individuals and intra-individually (p〈0.05). Urinary tienilic acid level and natriuretic effect were correlated, too (p〈0.05 top〈0.001), but only intraindividually. No correlation between drug level and uricosuric effect was found.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609624
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  • 193
    Digitale Medien
    Digitale Medien
    Pharmakokinetic properties of noscapine (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 535-539 
    Details
    ISSN: 1432-1041
    Schlagwort(e): noscapine ; pharmacokinetics ; absorption ; bioavailability ; intravenous application ; oral application ; ion exchange resin tablet
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Noscapine was administred to five healthy volunteers in a randomized crossover design, as an intravenous infusion of 66 mg, and as an oral 150 mg dose of either rapidly dissolving tablets or a tablet containing ion exchange resin-bound noscapine. After i.v. administration, the disposition of noscapine was bi-exponential with an elimination half-life of 2.6 h; the total plasma clearance was 22 ml/min/kg and the volume of distribution (Vdarea) was 4.7 l/kg. The absolute oral bioavailability was 30%, with a 3.6-fold interindividual variation. There was no pharmacokinetic evidence to support a prolonged action of the ion exchange resin tablet.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609627
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  • 194
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of theophylline in patients following short-term intravenous infusion (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 417-422 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; aminophylline ; obstructive airways disease ; short-term i.v. infusion ; log-normal distribution ; pharmacokinetics ; serum concentrations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Serum theophylline concentrations after intravenous administration of a new short-term infusion (Euphyllin® Kurzzeitinfusion) were measured in 50 out-patients with chronic obstructive airways disease (COAD). An intravenous infusion of theophylline ethylenediamine 480 mg (corresponding to approximately 350 mg anhydrous theophylline) in 50 ml isotonic solution was given in 20 min. Blood samples were taken beforehand and 25 to 30 min and 1, 3 and 6 h after starting the infusion. 86% of the patients had a one-hour serum level in the therapeutic range of 8–20 mg/l, and 2 h later, this was true of 64% of the patients. The short-term infusion was well tolerated, even in cases with unknown high pre-infusion serum levels. Pertinent pharmacokinetic parameters were determined, such as total body clearance, apparent volume of distribution, and half-life of elimination. Geometric mean and 95%-confidence limits, derived from the log-normal distribution of these parameters, were: Cl=0.044 (0.018–0.109) l/h/kg ideal body weight, Vd=0.451 (0.258–0.789) l/kg ideal body weight, and t1/2(el)=7.1 (2.6–19.1) h.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542546
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  • 195
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of bacmecillinam and pivmecillinam in volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 249-252 
    Details
    ISSN: 1432-1041
    Schlagwort(e): mecillinam ; bacmecillinam ; pivmecillinam ; pharmacokinetics ; pro-drug ; healthy volunteers ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of bacmecillinam and pivmecillinam were studied in healthy fasting volunteers given tablets in a cross-over, randomized order. The mean (±SD) peak levels of plasma mecillinam were 1.43±0.34, 2.73±0.43, and 4.62±1.41 mg/l after bacmecillinam 100, 200, and 400 mg and 2.38±0.65 mg/l after pivmecillinam 400 mg. The corresponding areas under plasma Vs time curves (AUC) were 2.21±0.19, 3.99±0.63, and 7.74±1.38 mg·h·l−1 for bacmecillinam and 5.35±0.93 mg·h·l−1 for pivmecillinam. The elimination half-lives were 0.8–1.1h for bacmecillinam and 0.7h for pivmecillinam. The 12 h urinary recovery of unchanged mecillinam after the 400 mg doses was 41% for bacmecillinam and 30% for pivmecillinam. The 400 mg dose of bacmecillinam gave a significantly higher plasma peak (p〈0.001), AUC (p〈0.001) and urinary recovery (p〈0.001) than did pivmecillinam 400 mg. The plasma peaks appeared earlier and the rate of absorption was higher after bacmecillinam than after pivmecillinam (p〈0.05). In conclusion, bacmecillinam had a better bioavailability than pivmecillinam in the tablet formulations studied. The AUC increased linearly with increasing doses of bacmecillinam.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00547563
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  • 196
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of terodiline in human volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 267-270 
    Details
    ISSN: 1432-1041
    Schlagwort(e): terodiline ; human volunteers ; pharmacokinetics ; serum clearance ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of terodiline HCl was studied in nine healthy volunteers given 12.5 mg i.v. and p.o. or 20 mg i.v. and 25 mg p.o. on two different occasions. The serum concentrations were measured by gas chromatography — mass spectrometry, using deuterated terodiline HCl as the internal standard. After i.v. administration the kinetics could be described by a two-compartment model with a mean distribution half life of 0.3 h and a mean elimination half life of 63 h. The serum clearance and apparent volume of distribution varied about 4-fold with mean values of 4.8 l/h and 417 l, respectively. After oral administration, the mean half life of absorption was 0.7 h and that of elimination 65 h. The absolute bioavailability varied between 64% and 105% with a mean of 92%. The long serum half life of terodiline should permit its once daily administration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00547566
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  • 197
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of pancuronium in man: A linear system (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 369-372 
    Details
    ISSN: 1432-1041
    Schlagwort(e): neuromuscular blockade ; pancuronium ; non-depolarizing neuromuscular blocking agent ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pancuronium in bolus doses of 40 to 350 µg/kg was administered to surgical patients in order to evaluate the linearity of its pharmacokinetics. The profile of the plasma decay curve and of its urinary elimination were compared with reference to the administered dose. It was possible to superimpose the dose-normalized plasma decay-curves. The parameters of the two compartment-open model used to describe the pharmacokinetics of pancuronium were not influenced by the dose. The elimination half-life was 89±20 min and the plasma clearance was 1.84±0.38 ml/min/kg. The profiles of cumulative urinary excretion were also dose-independent. After 6 and 24 h, 57% and 69% of the administered dose, respectively, had been excreted in the urine. The results indicate that the pharmacokinetics of pancuronium is linear.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613623
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  • 198
    Digitale Medien
    Digitale Medien
    Influence of acetylator phenotype on the pharmacokinetics of a new vasodilator antihypertensive, endralazine (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 523-527 
    Details
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; acetylator phenotype ; hydralazine ; pharmacokinetics ; plasma concentrations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five and 10 mg single oral doses of a new vasodilator antihypertensive, endralazine (E) were given on separate occasions to 17 normal male volunteers (8 slow, 7 heterozygous fast and 2 homozygous fast acetylators). The homozygous fast acetylators were excluded from statistical comparisons. Only small differences were observed in the pharmacokinetics of E between the phenotypes and there was no evidence of non-linearity at the 2 dose levels studied. Terminal half-lives ranged from 2.59 to 7.14 h with a mean of 4.30±1.08 h for the 5 mg dose and 4.25±1.09 h for the 10 mg dose. There was no significant difference in half-lives between slow and heterozygous fast acetylators. The mean area under the plasma level-time curve (AUC 0 ∞ ) was 18.2% lower (p〈0.05) in the heterozygous fast acetylators than in the slow acetylators following the 5 mg dose and 11.0% lower (p〉0.05) following the 10 mg dose. Extremely rapid absorption of the drug precluded accurate estimation of absorption rates. The AUC 0 ∞ of the acetylation metabolite (methyltriazoloendralazine) was small compared to that of E although higher in the heterozygous fast acetylators than in the slow acetylators (p〈0.01).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637500
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  • 199
    Digitale Medien
    Digitale Medien
    Estimation of absorption ratios and their variation for orally administered drugs (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 265-272 
    Details
    ISSN: 1432-1041
    Schlagwort(e): pharmacokinetics ; variation of absorption ratios ; bioavailability ; dissection of variation due to absorption and intermediate processes ; oral drug application
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Differences in the plasma concentrations of drugs after oral administration are caused by two main factors: variation in absorption ratios and in the distribution processes in the body. A new method for the dissection of both types of factors is discussed. The method uses a reference regression of the AUC-values to the corresponding values after intravenous infusion of graded doses. The reference regression is estimated from an appropriate trial. Deviation of the determined AUC-values from the regression curve afford an estimate of the residual variance due to varying distribution volumes or similar random biological effects. For the estimation of absorption ratios after oral administration the drug is given orally to another sample of subjects and their AUC-values are calculated. The deviation of these AUC values due to the above mentioned random effects are simulated using the residual variance of the reference regression, and are subtracted from the observed AUC-values. Then, the differences in the corresponding absorbed doses are transformed by inverting the reference regression. From these doses the empirical distribution function and statistical parameters (e.g. quantiles) are determined. The method has the advantage that no restrictive assumptions are required, such as first order processes, dose linearity, homogeneity of variance or normal distribution of absorption ratios. Its applicability to substances with qualitative differences in their pharmacokinetics is demonstrated by appropriate examples.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00545226
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  • 200
    Digitale Medien
    Digitale Medien
    Effect of urinary pH on the disposition of methadone in man (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 337-342 
    Details
    ISSN: 1432-1041
    Schlagwort(e): methadone ; pharmacokinetics ; urinary pH ; RBC level ; saliary level ; mass fragmentography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of urinary pH on the acute disposition of methadone in man was studied in five healthy volunteers. A cross-over experiment was performed in each subject. In the first experiment the subjects were treated with ammonium chloride (urinary pH ≈ 5.2) and in the other the urine was made alkaline (pH ≈ 7.8) by treatment with sodium hydrogen carbonate. d, 1-Methadone-HCl 10 mg (M) was administered intramuscularly on each occasion and blood, saliva and urine levels of M were determined by mass fragmentography. Plasma half-lives, volumes of distribution and body clearances of M were calculated in both experiments. The plasma half-lives in the β-phase were 19.5±3.6 h (acidic urine) and 42.1±8.8 h (alkaline urine), respectively (p〈0.001). The volumes of distribution were increased when the pretreatment was changed from ammonium chloride to sodium bicarbonate, namely from 3.51±0.41 l/kg to 5.24±0.83 l/kg (p〈0.01). The body clearance decreased from 134±21 ml/min (acidic) to 91.9±9.1 ml/min (alkaline urine) (p〈0.01). The ration Mplasma/MRBC was about 2.3 and the elimination of M from RBCs was in good agreement with the plasma kinetics of M under both experimental conditions. The salivary levels of M did not reflect the plasma kinetics and considerable variation was seen in the ratio Msaliva/Mplasma (0.26–2.98). Thus, the present experiments demonstrate that pretreatment either with ammonium chloride or bicarbonate had profound effects on both the distribution and elimination kinetics of methadone.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548403
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