Bibliothek

Ihre E-Mail wurde erfolgreich gesendet. Bitte prüfen Sie Ihren Maileingang.

Leider ist ein Fehler beim E-Mail-Versand aufgetreten. Bitte versuchen Sie es erneut.

Vorgang fortführen?

Exportieren
Filter
  • Digitale Medien  (4.529)
  • 2020-2023
  • 2000-2004  (78)
  • 1985-1989  (3.379)
  • 1975-1979
  • 1890-1899  (749)
  • 1870-1879  (323)
  • 2000  (78)
  • 1987  (1.478)
  • 1985  (1.901)
  • 1898  (749)
  • 1870  (323)
  • Inorganic Chemistry  (2.515)
  • Biochemistry and Biotechnology  (1.017)
  • Physics  (479)
  • Life Sciences  (261)
  • pharmacokinetics  (257)
Materialart
  • Digitale Medien  (4.529)
Erscheinungszeitraum
  • 2020-2023
  • 2000-2004  (78)
  • 1985-1989  (3.379)
  • 1975-1979
  • 1890-1899  (749)
  • +
Jahr
Schlagwörter
  • 101
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 499-504 
    ISSN: 1432-1041
    Schlagwort(e): morphine ; epidural administration ; pharmacokinetics ; CSF/plasma concentrations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In order to determine the rate and degree of redistribution of morphine within the cerebrospinal fluid (CSF), and whether it was affected by the site of and volume of the injection, morphine was given to 23 elderly patients undergoing thoracotomy — in 10 ml saline in the lumbar epidural interspace (n=5), in 10 ml saline in the thoracic epidural interspace (n=5), in 2 ml saline in the thoracic interspace (n=8) and in 10 ml saline in the lumbar epidural interspace (n=5). The plasma concentration of morphine in all patients was comparable and was much lower than in the CSF. The CSF morphine concentration, measured as the area under the CSF concentration curve (AUC), the maximal CSF concentration (Cmax) and the time to reach maximal CSF concentration (tmax), varied between the four groups. The variation was related to the site of the injection; the AUC and Cmax were lower and tmax appeared later after thoracic than lumbar injection. Lumbar CSF morphine concentrations were further reduced by thoracic epidural injection of morphine in a small as compared to a large volume. The permeability of the dura to morphine was not influenced by the volume used. The results show that morphine is not homogenously distributed within the CSF. The availability of morphine to CSF from the epidural space is not altered by the injection volume, but the drug remains more localized in CSF after epidural injection of morphine in a small volume. The findings imply that epidural injection of morphine in a small volume at a site of nociceptive input should evoke spinal analgesia with least risk of supraspinally mediated side effects.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 102
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 273-277 
    ISSN: 1432-1041
    Schlagwort(e): pentobarbital ; hexobarbital ; dipyrone ; intensive care ; D-glucaric acid ; pharmacokinetics ; drug interactions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of pentobarbital treatment in a mean dose of 30 mg/kg/day on the clearance of hexobarbital (Evipan) and dipyrone (Novalgin) has been evaluated in critical care patients receiving a large number of drugs as comedication. Eleven patients treated with pentobarbital showed a hexobarbital half-life of 2.79 h and a total plasma clearance of 9.80 ml·min−1·kg−1 as compared to 10 patients without pentobarbital administration in whom there was a significantly longer half life (6.92 h) and lower clearance (2.97 ml·min−1·kg−1). The kinetics of hexobarbital were correlated with the urinary excretion of D-glucaric acid, a non-invasive parameter of drug metabolising activity. In 10 patients on pentobarbital, the total plasma clearance of N-4-methylaminoantipyrine, the active form of dipyrone, did not differ from that in 8 patients not receiving pentobarbital. As drug kinetics show great variability in these patients, it is difficult to discriminate enzyme induction from other mechanisms, for example competitive inhibition or changes in volume of distribution. In the presence of pentobarbital, however, induction of drug metabolising enzymes should be considered as a possible reason for the higher clearance of hexobarbital.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 103
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 367-372 
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; severe hypertension ; food intake ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A sensitive HPLC assay has been used to determine the effect of food on plasma endralazine levels in 8 patients with essential hypertension. Subjects were investigated whilst on maintenance therapy with endralazine combined with a fixed antihypertensive baseline treatment for at least 4 weeks, samples being collected after the usual oral morning dose of endralazine (5 mg and 10 mg), on two occasions at least 7 days apart. Endralazine was administered with the concomitant therapy in randomised order once 90 min before and once immediately after a standard breakfast. Acetylator status did not affect its pharmacokinetics in the postprandial study after a 5 mg dose, the peak endralazine concentration averaged 57.5% lower and the AUC had fallen significantly by 49.9%, whereas after 10 mg the postprandial peak level and the AUC were 82.9% and 64.7%, lower. In the 5 mg study the mean arterial blood pressure was decreased by 30 mm Hg in the fasting subjects and by 21 mm Hg in the post-prandial group. For the 10 mg dose the corresponding values were 35 and 24 mm Hg. The blood pressure lowering effect was only weakly correlated with the food — related reduction in the plasma endralazine levels. The results suggest that endralazine has a similar kinetic interaction with food as that found for hydralazine.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 104
    ISSN: 1432-1041
    Schlagwort(e): triazolam ; troleandomycin ; benzodiazepines ; antibiotics ; drug interaction ; pharmacokinetics ; first-pass effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Seven healthy volunteers received a single oral dose of triazolam 0.25 mg after 7 days on troleandomycin 2 g/day p.o. or placebo in a double-blind cross-over study. Plasma triazolam and psychometric and memory tests (including Critical Flicker Fusion threshold, Choice Reaction Time, Digit Symbol Substitution and Self-Rating Scales) were assessed at regular intervals after the final treatment. Troleandomycin was found to prolong the psychomotor impairment and amnesia produced by triazolam. There was a significant enhancement of the AUC, the peak concentration and the delay to tmax of triazolam after 7 days treatment with troleandomycin compared to placebo. Thus, there is a pharmacokinetic interaction, and the combination of triazolam and troleandomycin should be avoided or the dose of triazolam should be adjusted. The most likely mechanism is a diminished hepatic first-pass effect, and a decrease in the apparent oral clearance of triazolam.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 105
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 577-582 
    ISSN: 1432-1041
    Schlagwort(e): yohimbine ; pharmacokinetics ; plasma levels ; renal elimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetic disposition of yohimbine was examined in eight young male subjects following a single oral dose of 10 mg yohimbine hydrochloride. The drug was rapidly absorbed (absorption half-time 0.17±0.11 h) and rapidly eliminated from the plasma (elimination half-life 0.60±0.26 h). This clearance of yohimbine from plasma was constant over approximately 10 elimination half-lives, suggesting that distribution into a second pharmacokinetically distinct compartment was not responsible for the rapid decline in plasma yohimbine levels. Urinary excretion and the partitioning of the drug into red blood cells (RBC) was investigated. In the 24 h following oral administration of the drug, virtually no yohimbine was eliminated in the urine (0.35±0.50% of the administered dose). Furthermore, only 20% of blood-borne yohimbine was located in RBC. These results suggest that yohimbine is eliminated primarily through metabolism since the rapid plasma clearance of yohimbine was not the result of renal elimination or sequestration by RBC.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 106
    ISSN: 1432-1041
    Schlagwort(e): moracizine·HCl ; antiarrhythmic ; ethmozine ; radiolabelled ; pharmacokinetics ; material balance ; healthy subjects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Moracizine (ethmozine) is a phenothiazine derivative with demonstrated antiarrhythmic activity. To characterize the pharmacokinetics and material balance relationships in humans, we have given14C-moracizine·HCl as a single oral dose of 500 mg (50 μCi) to six healthy men. Plasma, urine, and faecal samples were collected for 7 days after administration and the concentrations of total radioactivity and intact moracizine were determined by liquid scintillation counting and HPLC, respectively. Urine and faecal recovery accounted for 95% of the administered radioactivity. Most of this radioactivity was found in the faeces (59%). Only 0.05% of the dose was recovered from urine as intact moracizine. The Cmax and AUC for moracizine equivalents of total radioactivity were 4- and 18-fold higher, respectively, than the corresponding values for intact moracizine. Additionally, both the disappearance of total radioactivity from plasma and its excretion rate into urine were slower in comparison to intact drug. Terminal t1/2 values calculated from plasma concentration-time data were 85.2 and 3.5 h for total radioactivity and intact moracizine, respectively. However, based on urinary excretion rates, the t1/2 for total radioactivity was shorter (29.3 h) while the t1/2 for intact drug was comparable (2.7 h) to the results obtained from the plasma data. The oral plasma clearance of moracizine was relatively large (2.2l·min−1), suggesting first-pass metabolism. The estimated oral systemic availability of moracizine was 34%.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 107
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 711-714 
    ISSN: 1432-1041
    Schlagwort(e): flecainide ; pharmacokinetics ; moderate renal failure ; variability of elimination half-time
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the pharmacokinetics of flecainide after the oral administration of 100 mg to 8 patients without renal impairment and 8 patients with mild to moderate renal failure. Both groups gave comparable results with respect to the peak plasma concentrations and the time to peak. There was a significant correlation between renal flecainide clearance and endogenous creatinine clearance. The elimination half-time in the patients with impaired renal function was significantly longer (19.9, SD 9.9 h) than that in the patients with normal renal function (11.5, SD 4.2 h), but the variability in the elimination half-time in renal failure could not be explained on the basis of the available results.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 108
    ISSN: 1432-1041
    Schlagwort(e): captopril ; uraemia ; captopril disulfide ; dialysis ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have measured the plasma concentrations of captopril and total disulfide conjugates of captopril after a 50 mg oral dose in 6 uraemic patients on maintenance dialysis and in 8 hypertensive subjects with normal renal function. The mean peak plasma concentration of captopril was 2.5 times higher (0.447 µg·ml−1 vs 0.181 µg·ml−1) and the concentrations of the disulfides 4 times higher (3.62 µg·ml−1 vs 0.924 µg·ml−1) in the uraemic patients. Moreover captopril disulfide conjugates in the uraemic subjects reached peak concentrations at 8 h after the dose and subsequently felt. The apparent plasma half-time was 46±19 h. Only 15% of these conjugates were removed by dialysis. This marked accumulation of captopril conjugates was associated with a sustained fall in both systolic and diastolic blood pressures. In uraemic patients the mean maximum reduction in systolic and diastolic blood pressures were 37±7 mmHg and 24±9 mmHg respectively, occurring 6 h after the dose, compared with 8±7 and 8±1 mmHg respectively at 30 min in normal renal function patients. These results are consistent with the results of animal experiments, which show that captopril disulfides can be converted back to free captopril and can contribute to the antihypertensive effect of the drug. They provide a reationale for reducing the dose and frequency of administration of captopril in patients with significant renal impairment.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 109
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 309-311 
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; verapamil ; cirrhosis ; drug interaction ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of a single low dose of verapamil (80 mg) on the serum levels of digoxin (single dose of 0.5 mg) was studied in 6 patients with hepatic cirrhosis and in 6 healthy volunteer controls. In the cirrhotic patients verapamil increased the peak serum level and the total AUC of digoxin by 98% and 32%, respectively. There was an associated 23% decrease in the renal digoxin clearance. In normal subjects only marginal alterations in digoxin kinetics were observed following verapamil administration. The results indicate that cirrhosis magnifies the influence of verapamil on digoxin kinetics.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 110
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 303-307 
    ISSN: 1432-1041
    Schlagwort(e): azapropazone ; arthritis ; pharmacokinetics ; synovial fluid level ; synovial tissue level
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The concentration-time curves of azapropazone in synovial fluid and tissues have been studied in arthritic patients after an i.v. bolus (600 mg) and under steady-state conditions. Synovial fluid and tissue samples were taken intraoperatively 0.45–60 h after administration. The azapropazone concentrations in synovial fluid, synovial tissue and plasma were correlated. The levels in synovial fluid were usually lower than corresponding plasma levels. Under steady-state conditions azapropazone did not accumulate in synovial tissues.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 111
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 317-320 
    ISSN: 1432-1041
    Schlagwort(e): ranitidine ; amitriptyline ; drug interaction ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The possibility of an interaction of ranitidine with amitriptyline was assessed by means of amitriptyline and nortriptyline plasma concentration measurements, blood pressure and pulse rate, digit symbol substitution, and visual analogue scales. Ranitidine had no effect on amitriptyline or nortriptyline concentrations. Responses recorded by the digit symbol substitution and visual analogue scale tests correlated with changes in concentrations of amitriptyline and nortriptyline in plasma. No effects on blood pressure or pulse rate were observed. We concluded that there was no effect of ranitidine on amitriptyline kinetics or response in the conditions of our study.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 112
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 351-355 
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; cimetidine ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma pharmacokinetics of nifedipine and the formation of its metabolites have been studied in volunteers under conditions which would affect the activity of the cytochrome P-450 system. The pharmacokinetics of a 10-mg capsule of nifedipine were not significantly different between smokers and non-smokers of similar age. After pretreatment with cimetidine, which inhibits the activity of cytochrome P-450, the peak plasma concentration and area under the plasma-time concentration curve for nifedipine were increased by a mean 84%. In contrast, pre-treatment with ranitidine which has little effect on cytochrome P-450, did not significantly alter nifedipine pharmacokinetics. Smoking does not contribute significantly to the variability in nifedipine pharmacokinetics. However, the interaction between nifedipine and cimetidine, but not ranitidine, may be of clinical importance.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 113
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 377-382 
    ISSN: 1432-1041
    Schlagwort(e): morphine ; renal failure ; pharmacokinetics ; morphine-3-glucuronide
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of morphine and its glucuronidated metabolites were investigated in seven patients with advanced renal failure. The terminal elimination half life of morphine varied between 1.5 and 4.0 h (mean 2.4 h), the volume of distribution between 2.5 and 6.3 l·kg−1 (mean 4.4 l·kg−1) and the total plasma clearance between 13.3 and 31.3 l·min−1·kg−1 (mean 21.1 l·kg−1). There were no statistically significant differences between the pharmacokinetic data in the uraemic patients and in a control group of cancer patients with normal kidney function. The concentrations of the glucuronidated metabolites rapidly rose to levels above those of morphine. The elimination half-life of M3G varied between 14.5 and 118.8 h (mean 49.6 h) in the renal failure patients, which is distinctly different from the 2.4 to 6.7 h (mean 4.0 h) found in patients with normal kidney function. There was a significant correlation between the half-life of M3G and renal function estimated as serum urea. Thus, the metabolism of morphine in patients with kidney disease is not significantly impaired. The clinical importance of the high concentrations of glucuronides in uraemic patients is not known.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 114
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 395-401 
    ISSN: 1432-1041
    Schlagwort(e): probenecid ; Michaelis-Menten kinetics ; protein binding ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six healthy volunteers were given probenecid 0.5, 1 and 2 g p.o. and 0.5 g i.v. The protein binding of probenecid at different concentrations in human plasma was estimated by equilibrium dialysis. The free fraction was found to increase nonlinearly with increasing total probenecid concentration, up to a maximum free fraction of 26%. The plasma concentration-time data after the oral doses were described by a one-compartment open model with first-order absorption and Michaelis-Menten elimination. The mean absorption rate constant 0.0072 min−1 was dose-independent, and the maximal rate of elimination (mean 1429 µg/min) did not differ between doses whether calculated from the total or free concentrations. The Michaelis-Menten constant decreased significantly from 67.1 to 55.5 µg/ml as the dose increased from 1 g to 2 g, while the unbound Michaelis-Menten constant remained unchanged. The elimination of probenecid after the 0.5 g dose was in the linear region of the Michaelis-Menten elimination when calculated from the total and the free concentrations. The volume of distribution increased only slightly from 9.5 to 11.4 l as the dose increased from 0.5 to 2 g, but the unbound volume of distribution decreased significantly from 164 to 99 l. Absorption was complete and was independent of the dose administered.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 115
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 667-672 
    ISSN: 1432-1041
    Schlagwort(e): adrenergic beta-receptors ; propranolol ; beta-blockade ; pharmacokinetics ; leukocyte beta-receptors ; leukocytes ; exercise tachycardia ; 4—OH-propranolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The chronotropic response to a single oral dose of propranolol in 23 healthy subjects has been related to the plasma propranolol concentration and the density of β-adrenoceptors on peripheral polymorphonuclear leucocytes. The percentage reduction in exercise-induced tachycardia was significantly correlated with the log plasma propranolol concentration within subjects but not between subjects. Taking the concentration of the active metabolite 4-hydroxypropranolol into account did not improve the interindividual correlation. The reduction in exercise-induced tachycardia was significantly correlated with the maximum binding density of (125I)-hydroxybenzylpindolol on polymorphonuclear leucocyte membrane fragments measured before medication. A response index (% reduction in exercise-induced tachycardia/plasma propranolol concentration) was correlated with the maximum binding density of (125I)-hydroxybenzylpindolol (predrug) at 2 h (rs=0.72), 4 h (rs=0.84) and 6 h (rs=0.73) after dosing. The data suggest that interindividual variation in the response to propranolol after a single oral dose is determined by interindividual differences both in plasma propranolol and adrenoceptor density.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 116
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 695-699 
    ISSN: 1432-1041
    Schlagwort(e): doxorubicin ; sarcoma ; pharmacokinetics ; polychemotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of doxorubicin has been studied in 26 sarcoma patients receiving polychemotherapy. Mean elimination half-life was 34.7±16.6 h and the total plasma clearance was 29.5±9.31·h−1·m−2. No relationship was found between the pharmacokinetic parameters and the response to treatment, or its toxicity. Special attention was paid to the early-phase kinetics of the drug (3–20 min after injection). A correlation between the early clearance and the ages of the patients was observed. The early clearance was clearly correlated with the total plasma clearance measured over 48 h after injection, indicating the importance of the distribution phase in the overall kinetics of the drug.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 117
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 701-704 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; miocamycin ; drug interaction ; metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The interaction between a new macrolide antibiotic, miocamycin, and theophylline was evaluated in a single cross-over study in 5 asthmatic children. Each patient received a single dose of theophylline (4.3 mg/kg) delivered in 15 min using a constant-rate infusion pump, immediately before and after a 10 day course of miocamycin 17.5 mg/kg b.d. The pharmacokinetics of theophylline were calculated for each phase of the study. The elimination rate constant (3.92 vs 3.74 h−1), the mean total body clearance (1.71 vs 1.8 ml·min·kg−1) and the mean apparent volume of distribution (0.57 vs 0.58 l·kg−1) did not differ. The result can be explained by the inability of the antibiotic to form inactive cytochrome P-450 metabolite complexes which can interfere with the metabolism of theophylline. Thus, miocamycin can safely be administered to asthmatic children requiring theophylline treatment, when they have an infection due to susceptible pathogens.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 118
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 733-736 
    ISSN: 1432-1041
    Schlagwort(e): meptazinol ; pharmacokinetics ; elderly patients ; healthy volunteers ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have determined the pharmacokinetics of meptazinol after its intravenous and intramuscular administration in a crossover study in 7 elderly hospital in-patients (〉70 years), and have compared with the results from 14 healthy, young volunteers (ages 20–40 years). The systemic availability after i.m. administration was comparable to that after i.v. administration, a result consistent with the physicochemical properties of the drug. There was a slight, but statistically significant (p〈0.01) prolongation in t1/2z in the elderly (mean 2.93 h) compared with the young (mean 2.06 h). This was associated with a 25% lower clearance in the elderly rather than with any alteration in volume of distribution. However, these changes would not appear to be substantial enough to require a revised dosage recommendation for meptazinol for this age group.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 119
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 743-743 
    ISSN: 1432-1041
    Schlagwort(e): chloroquine ; dose dependence ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 120
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 17-22 
    ISSN: 1432-1041
    Schlagwort(e): felodipine ; calcium antagonist ; normal man ; renal function ; albumin excretion ; beta2-microglobulin excretion ; adverse effects ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The acute renal effects of a single oral dose of felodipine 0.15 mg/kg were studied in 8 healthy males. Thirty minutes after administration the mean plasma concentration was 25.7 nmol/l. There was a significant reduction in diastolic blood pressure (24%) and a concomitant rise in heart rate (38%), leaving the systolic pressure unchanged. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique using the clearance of125I-iothalamate and131I-hippuran respectively. GFR was unchanged and the filtration fraction (FF) was reduced, whilst there was a decrease in renal vascular resistance (RVR). The glomerular filter characteristics were unchanged, as estimated by the unchanged excretion rate of albumin. There was a significant rise in the clearance of sodium (176%) but only a small and insignificant increase in urine volume. Clearance of potassium was decreased. An increase in the clearance of uric acid and a rise in the beta-2-microglobulin excretion rate were found, both suggesting a proximal tubular effect of felodipine. The excretion rate of calcium was increased.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 121
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; amiloride ; hydrochlorothiazide ; young ; elderly ; pharmacokinetics ; pharmacodynamics ; volunteers ; patients ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six normal young and six normal elderly volunteers and six elderly hypertensive patients took part in an acute and chronic dose study of a combination capsule containing atenolol (50 mg), hydrochlorothiazide (25 mg) and amiloride (2.5 mg) designed for the treatment of hypertension. No difference in any of the drug pharmacokinetic parameters could be detected between the hypertensives and the normal elderly subjects. The bio-availability and the 24-h blood concentrations of all three drugs, half-life of atenolol and amiloride and the peak concentration of hydrochlorothiazide was significantly greater in the elderly. The 24-h blood concentrations of atenolol and hydrochlorothiazide did not alter with chronic dosing, but amiloride concentrations were significantly higher at this time in all groups. A significant fall in the blood pressure was observed in the hypertensive group. Heart rate fell more in the normal and hypertensive elderly subjects than in the young. The combination has shown to be an effective and well tolerated antihypertensive in the elderly patient with a 24-h duration of action.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 122
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 165-172 
    ISSN: 1432-1041
    Schlagwort(e): warfarin ; cimetidine ; ranitidine ; stereochemistry ; drug-drug interaction ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Stereochemical aspects of the potential interaction between the oral anticoagulant warfarin and the H2-antagonists, cimetidine and ranitidine, were investigated. A single 25 mg oral dose of racemic warfarin was administered on Day 4 of a randomised 9-day multiple dosing regimen of either cimetidine (800 mg o.d.) ranitidine (300 mg o.d.) or placebo. The degree of anticoagulation produced by warfarin was quantificated by the determination of both the prothrombin and Factor VII clotting times. Ranitidine had no effect on the pharmacodynamics of warfarin or the pharmacokinetics of the individual warfarin enantiomers. Cimetidine whilst producing no statistically significant change in the pharmacodynamics of warfarin or in the pharmacokinetics of the pharmacologically more potent (S) enantiomer, did produce a statistically significant decrease in the clearance of the (R) enantiomer, possibly due to metabolic inhibition of this species.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 123
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 357-360 
    ISSN: 1432-1041
    Schlagwort(e): nitrendipine ; food intake ; pharmacokinetics ; variability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations of nitrendipine were measured, after single (20 mg) oral doses, in young healthy volunteers. On three occasions the subjects ingested the dose having fasted overnight. Data from these three occasions were used to assess variability in nitrendipine pharmacokinetics and both inter- and intra-subject variability were high. On a fourth occasion, the subjects took the tablet after a standard meal. The effects of food on nitrendipine pharmacokinetics, based on the comparison of data from the first fasting visit and the food visit, were negligible.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 124
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 583-586 
    ISSN: 1432-1041
    Schlagwort(e): tiapride ; Huntington's disease ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic properties of a single oral dose of 100 mg of tiapride were studied in six patients with Huntington's disease. The results for five patients were consistent with a two compartment open model. Peak plasma concentrations were observed within 2 h following durg administration with a mean value of 0.92 μg/ml being recorded. The drug was rapidly eliminated as unmetabolised tiapride in the urine, 51% of the dose was recovered in 24 h. The plasma elimination half-life was 5.3 h and the average apparent plasma clearance was 16.6 l/h.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 125
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 593-596 
    ISSN: 1432-1041
    Schlagwort(e): dexamethasone ; dexamethasone phosphate, antiemetic ; pharmacokinetics ; cancer chemotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have given single high doses of dexamethasone phosphate by intravenous infusion as an antiemetic to 15 cancer patients receiving regimens containing cisplatin and/or doxorubicin. The patients received graded doses of dexamethasone phosphate, in the range 40–200 mg, dependent upon nausea and vomiting scores, during up to three consecutive cycles of cancer chemotherapy. Plasma and urine concentrations of dexamethasone (dexamethasone alcohol) were measured by HPLC. The plasma concentration-time data were described by an open two-compartment model. The pharmacokinetic variables were independent of the dose of dexamethasone over the range studied. The terminal half-time was 4.0±0.4 h and the total body clearance was 3.5±0.4 ml·min−1·kg−1. The volume of the central compartment and the total apparent volume of distribution were 0.23±0.03 and 1.0±0.1 l·kg−1 respectively. Approximately 8% of the dose was excreted into the urine as dexamethasone.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 126
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 617-619 
    ISSN: 1432-1041
    Schlagwort(e): chronopharmacology ; indomethacin ; suppository ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a single 100 mg indomethacin suppository were studied in 12 healthy volunteers on two occasions at least 7 days apart. Suppositories were administered in randomised order at 9.00 and 21.00 hours to see if there was evidence of a diurnal variation in kinetic parameters. The study failed to show a significant change in single dose kinetics with the time of suppository administration. This is in contrast to previous work [1] demonstrating a circadian rhythm in the kinetics of a single oral dose of indomethacin. This suggests that the chronopharmacokinetics of indomethacin is dependent on the function of the upper gastrointestinal tract.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 127
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 625-627 
    ISSN: 1432-1041
    Schlagwort(e): verapamil ; breast milk ; norverapamil ; breast feeding ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The concentrations of verapamil and norverapamil have been measured in milk and plasma samples from a 32year-old woman treated with verapamil 80 mg tds while breast-feeding her child. The average steady-state concentrations of verapamil and norverapamil in milk were, respectively, 60% and 16% of the concentrations in plasma. The breast-fed child received less than 0.01% of the dose of verapamil given to the mother. No verapamil or norverapamil (〈1 ng/ml) could be detected in the plasma from the child.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 128
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 575-578 
    ISSN: 1432-1041
    Schlagwort(e): felodipine ; metoprolol ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary This double-blind, cross-over study in healthy male subjects evaluated the pharmacokinetics of felodipine and metoprolol given both separately and in combination. During three, five-day study periods, felodipine 10 mg b.d., metoprolol 100 mg b.d. and a combination of the two, were given in random order. There was at least a 7-day washout period between each pharmacokinetic study day. Plasma levels of unchanged felodipine and metoprolol were measured for 24 h after the last dose, on the 5th day of each treatment period. Eight subjects, aged 19–22 years, completed the study. Both felodipine and metoprolol, given alone and in combination, were well tolerated. None of the felodipine pharmacokinetic variables (tmax, Cmax, Cmin, AUC (0–12) and t1/2) changed significantly when felodipine and metoprolol were given in combination. Cmax and AUC (0–12) for metoprolol increased significantly when metoprolol and felodipine were combined, although tmax, Cmin and t1/2 for metoprolol remained unchanged. The changes in metoprolol pharmacokinetics induced by felodipine are small and unlikely to be clinically important.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 129
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 583-588 
    ISSN: 1432-1041
    Schlagwort(e): cotinine ; pharmacokinetics ; non-smokers ; absolute bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cotinine, the main metabolite of nicotine, was administered intravenously to healthy male non-smoking volunteers in doses of 5, 10 and 20 mg, and orally in doses of 10 and 20 mg. Intravenous administration was characterized by a dose-independent half-life of 12.2 h, mean residence time of 15.9 h, total clearance of 3.64 l h−1 and a volume of distribution of 56.5 l. Renal clearance was 0.46 l h−1 and approximately 12.0% of the dose was excreted unchanged in the urine. The mean absorption time after oral dosing ranged between 1 and 3 h, the peak concentration was reached within 45 min and the mean elimination half-lives were 12.9 and 11.7 h, respectively, after the 10 and 20 mg doses. Systemic bioavailability ranged between 0.84 and 1.11 following 10 mg and between 0.97 and 1.03 following the 20 mg dose. Mean urinary recovery and renal clearance were almost identical with the values after iv administration.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 130
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 595-600 
    ISSN: 1432-1041
    Schlagwort(e): caffeine ; exercise ; obesity ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of obesity, exercise, and the interaction of obesity and exercise were examined in 6 caffeine naive, untrained, nonsmoking, college males (3 lean (LV), 3 obese (OV)). Each subject received caffeine (oral, 5.83 mg·kg−1 lean body weight) or placebo (50 mg citrate) prior to 3 h of seated rest and prior to 90 min of treadmill walking (40% of their maximal aerobic power) followed by 90 min of seated recovery. Serum samples were collected at various times and analyzed for caffeine by HPLC. Pharmacokinetic analysis indicated that at rest, OV had a significantly higher absorption rate constant (Ka 0.0757 vs. 0.0397 min−1), lower elimination rate constant (Ke 0.0027 vs. 0.0045 min−1), and longer serum half-life (t1/2 4.37 vs. 2.59 h) in comparison to LV. In exercise, as well as at rest LV and OV had a large difference in the volume of distribution (43.2 vs. 101. 1) (rest, 54.1 vs. 103.1). Exercise consistently resulted in a decrease in the maximal serum concentration of caffeine and the area under the curve in OV while having no consistent effect on LV. The interactive effects of obesity and exercise could not be dissociated. However, these results demonstrate that both obesity and exercise have modified the pharmacokinetics of caffeine.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 131
    ISSN: 1432-1041
    Schlagwort(e): dextran ; hydroxyethylstarch ; haemodilution ; ischaemic stroke ; plasma viscosity ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 21 patients with ischaemic strokes we have monitored plasma viscosity, total plasma concentration, numeric average molecular weight (Mn), and weight average molecular weight (Mw) of Dextran 40 (dextran) and hydroxyethylstarch 200/0.5 (HES) during 10 days of treatment (days 1–4, 2×500 ml; days 5–10, 1×500 ml). Plasma concentrations of dextran increased during the first 4 days (8.3 mg·ml−1 on the first day to 18.0 mg·ml−1 on the fifth day), reached an apparent steady state of 17.2 mg·ml−1 during the next 6 days, and declined subsequently with a half-time (t1/2) of 4.03 days. After ten days treatment Mn and Mw were shifted towards higher values. Plasma viscosity increased from 1.26 mPas to 1.69 mPas on Day 10 (p〈0.01) and was linearly correlated with the total plasma concentration of dextran (p〈0.001; r=0.88). Total plasma concentrations of HES averaged 11.7 mg·ml−1 on Day 1 and 12.4 mg·ml−1 on Day 5. The molecular weight distribution did not change during the infusions but decreased in comparison with the administered solution. Plasma viscosity fell from 1.40 mPas to 1.30 mPas at Day 10 (p〈0.05) and was not related to the concentration of HES. The haemodiluting effect, as indicated by a decrease of the haematocrit, was 22% and 16.8% for dextran and HES respectively. These data suggest several advantages of HES compared with dextran in haemodilution therapy of ischaemic stroke.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 132
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 569-573 
    ISSN: 1432-1041
    Schlagwort(e): tolazoline ; neonates ; persistent fetal circulation ; pharmacodynamic effects ; pharmacokinetics ; pulmonary circulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of two doses of tolazoline have been compared in 2 groups of newborns suffering from the persistent fetal circulation syndrome. The effects on PaO2 and AaDO2 were similar in the 2 groups who received either a bolus of 1 or 0.5 mg·kg−1 tolazoline, followed by a continuous infusion of 1 or 0.5 mg·kg−1·h−1. The observed changes did not differ significantly from those previously observed in babies treated with 2 mg·kg−1. A rise in PaO2 and a reduction in AaDO2 were usually observed shortly after the bolus injection and at plasma levels between 1.5 and 4 µg·ml·−1. A progressive rise in plasma level over time occurred after 1 mg·kg−1 (and in the previous study of 2 mg) but not with 0.5g/kg tolazoline. The elimination half-life of tolazoline in 6 patients was 5 to 13 h. The data suggest that continuous infusion of tolazoline is not necessarily required and that the dose of 0.5 mg/kg is more appropriate and safer than the higher doses usually proposed.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 133
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 67-70 
    ISSN: 1432-1041
    Schlagwort(e): enprofylline ; pharmacokinetics ; elderly ; renal excretion ; half-life
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of enprofylline, a new potent antiasthmatic, has been studied in 20 healthy, elderly subjects, aged 65 to 81 years, and in 7 young adult controls, aged 23 to 37 years. The dose of 1 mg/kg body weight was given as an i.v. infusion. Plasma levels of enprofylline were followed for about 7 h and urine levels for 24 h. Both groups eliminated the major portion of the dose (about 83%) by renal excretion. As expected the mean creatinine clearance (92.5 ml·min−1· 1.73 m−2) was moderately decreased in the elderly subjects. The total clearance of enprofylline was 0.16 1·h−1·kg−1 and the renal clearance was 0.13 l·h−1·kg−1, which was significantly lower than that in the young controls (0.28 and 0.22 l·h−1·kg−1) respectively. Thus, the enprofylline clearance had fallen relatively more (about 40%) than the decrease in creatinine clearance (about 20%) with age. The half-life of enprofylline in old age was 2.5 h, which was significantly longer than in the younger adults (1.8 h). It is concluded that the pharmacokinetics of enprofylline was significantly influenced by advanced age, mainly due to reduced renal excretion. This reduction was more pronounced than anticipated from the age-dependent decline in creatinine clearance.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 134
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 103-106 
    ISSN: 1432-1041
    Schlagwort(e): fenoldopam ; peripheral dopamine agonist ; pharmacokinetics ; absorption ; food effects ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eight healthy volunteers participated in an open crossover study to assess the effect of a standardised meal on the systemic availability of a single oral dose of fenoldopam mesylate 100 mg. Subjects were studied on four separate occasions, twice fasting and twice fed in randomised, balanced order. Plasma and urine samples were obtained before and at regular intervals up to 25 h post dose. Measurement of fenoldopam (SK&F 82526) and its 8-sulphate metabolite (SK&F 87782) were by means of HPLC-EC analysis. Area under the plasma concentration time curve (AUC) and maximum detected plasma concentration (Cmax) for fenoldopam and SK&F 87782 were significantly reduced whereas time to maximum concentration was significantly increased with food. Using AUC's for fenoldopam and SK&F 87782, mean relative bioavailabilities were 35% and 81% respectively under fed compared with fasting conditions. Twenty-four hour excretion of fenoldopam was significantly reduced with food, but excretion of SK&F 87782 was apparently unchanged. Mean relative bioavailabilities calculated from these data were 83% and 86% respectively. Relatively large inter-subject variability in AUC and Cmax were seen, but intra-subject variability was not marked. Mild symptoms associated with vasodilation were reported on all study days.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 135
    ISSN: 1432-1041
    Schlagwort(e): mefloquine ; mefloquine/sulphadoxine/pyrimethamine ; Thai subjects ; pharmacokinetics ; drug interactions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of mefloquine were studied in 12 healthy Thai male and 12 healthy Thai female volunteers. Mefloquine (MQ) was administered either alone (750 mg orally) or in combination (MSP) with sulphadoxine (1.5 g) and pyrimethamine (75 mg) to each of 6 male and 6 female subjects. Plasma concentrations of MQ were measured by HPLC at intervals for 42 days. There was considerable interindividual variability in the pharmacokinetic parameters; for example in the male subjects receiving MQ alone peak concentrations ranged between 638 and 2494 ng·ml−1 with a mean concentration of 1442 ng·ml−1. Compared to previously published data on MQ concentrations in Caucasian male subjects, the present study indicates that higher concentrations are achieved in Thai subjects. The only significant difference in kinetic parameters between male and female subjects receiving MQ alone was in the mean residence time (MRT) which was greater in females. However, an analysis of pharmacokinetic parameters following administration of the combination preparation showed that the time to peak (tmax) was significantly reduced in females receiving MSP compared to the corresponding females given MQ alone and males given MSP. When data obtained from all subjects (male and female) receiving either MQ alone or MSP were combined, both MRT and half-life were significantly greater in subjects given MSP. There is therefore some evidence that therapeutic concentrations of MQ are maintained for a longer period of time following MSP administration.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 136
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 179-185 
    ISSN: 1432-1041
    Schlagwort(e): melphalan ; protein binding ; plasma ; humans ; rats ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The binding of melphalan to plasma proteins from four healthy humans and from rats was measured by centrifugal ultrafiltration. Melphalan concentrations were determined by HPLC and by measuring 14C-melphalan activity. In whole blood, melphalan was distributed preferentially in plasma. However, a constant fraction, 37%, which was independent of the total melphalan concentration in whole blood, was present within the red blood cells. The binding of melphalan to plasma proteins from humans was less than that from rats. In both, however, the fraction bound was constant throughout the concentration range (0.1 to 9.0 µM) that is achieved during standard-dose melphalan therapy. Albumin was the primary binding protein. At concentrations equal to or in excess of 33 µM, which have been achieved during high-dose melphalan therapy, free plasma melphalan concentrations were no longer linearly related to total drug concentrations, and the plasma protein binding of melphalan in the human became concentration dependent. This occurred at concentrations of 70 µM in the rat. Scatchard analysis of the data indicated the presence of 2 groups of binding sites. Class I sites had 0.03 and 0.4 binding sites per albumin molecule in humans and rats, with respective association constants of 4.43 × 104M−1 and 1.92 × 104M−1. Class II sites had 5.18 and 2.60 binding sites per molecule, with repective association constants of 3.82 × 102M−1 and 2.01 × 102M−1.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 137
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 203-205 
    ISSN: 1432-1041
    Schlagwort(e): paracetamol ; primaquine ; drug interaction ; metabolite formation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of paracetamol and the formation of metabolites were evaluated in 6 healthy volunteers before and during concomitant administration of a single dose (45 mg) of primaquine. There was no effect of the antimalarial drug on either conjugation (to paracetamol glucuronide and paracetamol sulphate) or oxidation (as judged by the presence of paracetamol cysteine and paracetamol mercapturate) pathways. Although primaquine inhibits certain oxidative metabolism (e.g. of antipyrine) it has no effect, in therapeutic doses, on paracetamol metabolism.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 138
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 211-215 
    ISSN: 1432-1041
    Schlagwort(e): diazepam ; pharmacokinetics ; Chinese ; white Caucasians ; body fat ; skin-fold thickness
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have compared diazepam pharmacokinetics in 16 Chinese and 18 white Caucasian healthy male volunteers, resident in Hong Kong and have correlated them with physical attributes. Serum concentrations of diazepam and desmethyldiazepam were measured in venous blood by an enzyme-linked immunoassay (0–3 h samples) and HPLC (3–72 h samples). Pharmacokinetic parameters were derived assuming a two compartment model, distribution phase 〈6 h, and 100% oral systemic availability. Compared with the Chinese the white Caucasians were older, heavier, taller, and fatter, as judged by skin fold thickness (SFT) and total body weight to ‘Ideal’ body weight (TBW/IBW) ratio; respective mean differences being 16%, 27%, 4%, 26%, and 15% (p〈0.05). Mean diazepam apparent volume of distribution (V) and V/IBW were larger in the white Caucasians (52% & 39% respectively, p=0.002). SFT and TBW/IBW ratio yielded the best correlations with V, V/TBW and V/IBW (0.50–0.75, p〈0.05). Obesity indices contributed most to the overall regressions (R2 up to 0.52), and for V there was a further small effect (2%, partial F test) due to ethnic group, possibly reflecting stature. Mean peak diazepam concentration (Cmax) was similar in both ethnic groups. Time to Cmax (tmax) was more often prolonged in the Chinese (X 2 test, p=0.01). Body fat and stature may thus account for these inter-ethnic differences in the apparent volume of distribution of diazepam, a highly lipid-soluble drug.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 139
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 259-265 
    ISSN: 1432-1041
    Schlagwort(e): ketanserin ; ketanserin-ol ; pharmacokinetics ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of ketanserin and its main metabolite ketanserin-ol, and the antihypertensive effects of intravenous, single oral and chronic oral (40 mg once daily) administration of ketanserin, have been investigated in a single blind study of 10 patients with uncomplicated mild hypertension. Ketanserin had a terminal half-life of 29.2 h, a plasma clearance of 518 ml/min and a volume of distribution of 18.0 l/kg. Chronic oral intake of 40 mg ketanserin (tablet formulation) gave a peak concentration of unchanged ketanserin of 88 ng/ml after 1.1 h. Its absolute bioavailability was 48%. During chronic therapy the maximal concentration of ketanserin-ol was 208 ng/ml and its half-life of elimination was 35.0 h. As this metabolite can be oxidized back to ketanserin, it contributes to the prolonged half-life of unchanged ketanserin seen during chronic therapy. The blood pressure was reduced by approximately 15% by oral ketanserin. The maximal reduction in blood pressure coincided with the peak concentration of unchanged ketanserin. During chronic therapy with 40 mg once daily blood pressure was reduced over 24 h. The heart rate was slightly reduced and the cardiovascular responses and the plasma noradrenaline concentrations during isometric exercise were only slightly influenced by ketanserin therapy. Thus, unchanged ketanserin has a relatively long half-life during chronic oral therapy and its pharmacokinetics in middle-aged hypertensive patients is similar to that in normal young volunteers.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 140
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 533-535 
    ISSN: 1432-1041
    Schlagwort(e): enprofylline ; children ; intravenous dose ; pharmacokinetics ; asthma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of intravenous enprofylline has been studied in 8 children with asthma. The mean plasma half-life of enprofylline (1.0 h) was considerably shorter than that previously reported in adults. The half-life determined from log urine excretion rate data was identical to the plasma half-life, so urine excretion could be used as a noninvasive method to study the elimination rate. As in adults, urinary recovery of unchanged drug averaged 89%, and the volume of distribution, Vz, averaged 0.58 l/kg. Clearance was higher in children than in adults when calculated per kg body weight, but not when calculated per m2 body surface area. The dosage of enprofylline in children would be more accurate if calculated in proportion to surface area rather than to body weight. Data agree with published information on creatinine clearance, which, adjusted for body surface area, stays constant from the age of 3 years until early adult life.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 141
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 89-91 
    ISSN: 1432-1041
    Schlagwort(e): antipyrine ; prednisolone ; pharmacokinetics ; obstructive lung disease ; hepatic drug metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of prednisolone on the elimination of antipyrine has been investigated. The one-sample antipyrine clearance was estimated in 23 outpatients with obstructive lung disease before and after treatment with prednisolone 30 or 50 mg/day for 7 days. During prednisolone administration antipyrine clearance decreased from 54.9±14.8 to 51.7±14.6 ml/min (mean±SD; p〈0.05). The results indicate that prednisolone decreases the rate of antipyrine elimination, but not to an extent suggesting a clinically important change in hepatic drug metabolism.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 142
    ISSN: 1432-1041
    Schlagwort(e): flecainide ; propranolol ; pharmacodynamics ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 143
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 101-104 
    ISSN: 1432-1041
    Schlagwort(e): enoxacin ; quinolone ; pharmacokinetics ; anti-bacterial ; elderly
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the pharmacokinetics of enoxacin in two groups of subjects, 10 young (18–45 years) and 10 elderly adults (〉65 years) after a single oral dose of enoxacin (600 mg). Enoxacin was absorbed rapidly, peak plasma concentrations being reached within two hours in both groups. However, the peak plasma concentration of enoxacin was significantly higher in the elderly than in the young adults. The area under the concentration-time curve extrapolated to infinity was also significantly greater in the elderly compared with the young subjects, and the apparent renal clearance was significantly less in the elderly than in the young adults. Consequently, the urinary elimination of unchanged enoxacin was significantly reduced in the elderly. The apparent volume of distribution in the elderly was significantly less than in the young adults. The elimination half-time of enoxacin was similar in the two groups.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 144
    ISSN: 1432-1041
    Schlagwort(e): buserelin ; LHRH superagonist ; histamine-induced rhinitis ; pharmacokinetics ; serum LH
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of experimental rhinitis on the absorption of buserelin, measured as the serum luteinizing hormone (LH) response, has been investigated. A single dose of 200 µg buserelin was given to 24 healthy male volunteers after induction of experimental rhinitis with histamine and after use of a saline spray (placebo control). Except on one occasion, when the pump-spray apparently was incorrectly operated, serum LH concentration rose after buserelin. There was no difference in the LH response between histamine-induced rhinitis and saline controls. It was concluded that intranasal application of buserelin represents a reliable mode of application and that modification of the administration route or a change in the dosage schedule during naturally-occurring nasal inflammations, such as the common cold and allergic rhinitis, is unnecessary in patients undergoing chronic treatment with intranasal buserelin, e.g. for prostatic cancer, endometriosis, precocious puberty, and contraception.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 145
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 185-189 
    ISSN: 1432-1041
    Schlagwort(e): vinpocetine ; apovincaminic acid ; healthy volunteers ; elderly subjects ; pharmacokinetics ; age effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of vinpocetine and its main metabolite, apovincaminic acid (AVA), were studied in the aged. Vinpocetine was eliminated with a mean half-life of 2.12±0.51 h. Total plasma clearance (CL) and distribution coefficient (Δ) of the parent drug were 2.2±0.9 l · kg−1 · h−1 and 6.7±3.7 l · kg−1, respectively. The CL and Δ of vinpocetine differed significantly from young subjects but the elimination half-life was not altered. Significant changes in the elimination half-life and plasma clearance of AVA were found, perhaps because of the physiological decrease in renal function.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 146
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 211-214 
    ISSN: 1432-1041
    Schlagwort(e): temazepam ; pharmacokinetics ; oral dose ; distribution half-life
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic disposition of temazepam was compared after a day-time and night-time dose in an open randomised crossover study. Twelve healthy male volunteers received a single oral dose of 20 mg temazepam in a soft gelatine capsule at 0900 h or 2200 h. Blood samples were taken immediately before dosing and at selected times over the 36-h period after each dose. The absorption of temazepam was slower after evening administration; the absorption half-life and time to reach maximal plasma concentration being 0.53 h and 1.67 h respectively, compared to 0.38 h and 1.02 h following morning administration. Considering distribution characteristics, evening administration produced a lower peak plasma temazepam concentration (362 ng/ml) compared with a day-time level of 510 ng/ml. Distribution half-life after night-time administration was increased compared with day-time administration (1.76 h vs 1.03 h). A significantly higher percentage of the drug, relative to Cmax, remained in the plasma at 8 and 24 h after evening dosing (39.3 and 15.4% compared to 24.7 and 11.2% following day-time administration). In spite of the half-lives of absorption, distribution and elimination all being longer after the evening dose, the overall bioavailability, as measured by the area under the curve (AUC) was comparable after the two times of administration. Similarly the difference in the mean residence time (MRT) of the two doses was within accepted limits. It is concluded that a chronopharmacokinetic effect was seen for temazepam; however it is unlikely to be of any clinical significance.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 147
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 237-242 
    ISSN: 1432-1041
    Schlagwort(e): thiazinamium ; asthma ; pharmacokinetics ; pharmacodynamics ; optimal concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and pharmacodynamics of thiazinamium (Multergan) were studied after intravenous and intramuscular administration to 7 males with chronic reversible airways obstruction. Disposition after i.v. administration was described by a clearance of 0.54 l·min−1, central compartment volume of 14.8 l, distribution rate constant 0.092 min−1, and an elimination rate constant of 0.0044 min−1. The corresponding estimates after i.m. administration were 0.324 l·min−1, 34.1 l, 0.035 min−1, and 0.0018 min−1. The bronchodilator response (expressed as % predicted FEV1) after i.v. administration was characterized by maximum increase in FEV1 of 33.9%, with an EC50 of 12.8 ng·ml−1 and an equilibration half-time of 11 min. Corresponding parameter estimates after i.m. administration were 32.2%, 18.8 ng·ml−1, and 9 min. Anticholinergic activity, measured by the change in heart rate after i.v. administration, showed maximum increase of 76 beats·min−1, with an EC50 of 176 ng·ml−1 and an equilibration half-time of 1.3 min. After i.m. administration the corresponding values were 120 beats·min−1, 250 ng·ml−1, and 3 min. The optimal plasma concentration of thiazinamium was about 100 ng·ml−1, which should give a near maximal bronchodilator response (over 80% of predicted normal) and a heart rate of about 100 beats·min−1.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 148
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 303-310 
    ISSN: 1432-1041
    Schlagwort(e): bendazac ; renal insufficiency ; pharmacokinetics ; bendazac-lysine ; 5-hydroxybendazac
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of bendazac and its major metabolite, 5-hydroxybendazac, have been investigated in 15 patients with moderate to severe renal insufficiency and renal failure following a single oral dose of 500 mg bendazac-lysine. The pharmacokinetic parameters were compared to those obtained in 10 healthy adult volunteers. The rate and the extent of absorption of bendazac was not modified in the patients with moderate and severe renal insufficiency, nor was there any change in plasma tmax, Cmax, apparent elimination t1/2 and AUC. There was a significant increase in the unbound fraction of bendazac in renal failure patients undergoing haemodialysis, with a consequent increase in the apparent volume of distribution (V/F) and apparent plasma clearance (CL/F), and a decrease in plasma Cmax and AUC. Simultaneous changes of V/F and CL/F lead to an unchanged plasma t1/2 in these patients. Renal clearance (CLR) was decreased, but CL/F was not affected, since renal excretion is a minor route of elimination of bendazac. Bendazac is mostly eliminated by metabolism to 5-hydroxybendazac, in healthy subjects 〉60% of a dose being excreted in urine as 5-hydroxybendazac and its glucuronide. In patients with renal insufficiency urinary excretion of 5-hydroxybendazac was decreased and the systemic availability of the metabolite (AUC), was increased about three-fold, irrespective of the degree of renal failure. Plasma 5-hydroxybendazac glucuronide accumulated according to the degree of renal insufficiency. Overall it can be assumed that the pharmacological effect of the drug will not be enhanced in renal failure and that the dosage regimen of bendazac-lysine in such patients need not be modified.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 149
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 369-373 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; omeprazole ; pharmacokinetics ; drug interaction ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a randomised double-blind cross-over study, 8 normal subjects received propranolol 80 mg twice daily with omeprazole 20 mg or identical placebo each morning. Propranolol kinetics were measured on day 8 of both treatment periods. Areas under the propranolol concentration/time curves were not significantly increased by omeprazole treatment: off treatment mean 787.6, on treatment 802.5 ng−1·ml·h. Maximum and minimum steady-state propranolol concentrations were similarily unaffected. Omeprazole also failed to increase the clinical effect of propranolol, as assessed by exercise tests on Day 8 of treatment. We conclude that omeprazole in the dose likely to be used for peptic ulcer has no significant effect on the kinetics or action of propranolol.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 150
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 391-396 
    ISSN: 1432-1041
    Schlagwort(e): metyrapone ; acetaminophen ; analgesic intoxication ; pharmacokinetics ; drug interaction ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary This study examined the effect of metyrapone on the elimination rate of acetaminophen and on the apparent formation rate of acetaminophen metabolites in man. Metyrapone treatment, 1.5 g, increased the half-life of acetaminophen, decreased the fraction of the dose recovered in the urine as the glucuronide and increased the fraction of the dose recovered in urine as the sulfate and mercapturate conjugates. The apparent rate constant for the formation of acetaminophen glucuronide was significantly decreased by metyrapone while the apparent rate constants for the formation of the sulfate and mercapturic acid metabolites were unchanged or slightly increased, respectively. These data indicate that metyrapone inhibits acetaminophen glucuronidation and possibly enhances the oxidation of acetaminophen to its quantitatively minor yet highly toxic reactive metabolite. The extent to which the parallel pathways of acetaminophen elimination are also affected by inhibitors of cytochrome P-450-mediated oxidation will limit the efficacy of these types of potential antidotes for the treatment of acetaminophen overdose.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 151
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 397-402 
    ISSN: 1432-1041
    Schlagwort(e): tolbutamide ; debrisoquine phenotype ; drug metabolism ; genetic polymorphism ; sulphonylureas ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The oxidative metabolism of tolbutamide was studied in 13 healthy subjects of known debrisoquine phenotype. Three were poor (PM) and ten were extensive (EM) metabolisers of debrisoquine. The mean values for total plasma clearance, elimination half-life, and metabolic clearance were 0.26 ml·min−1·kg−1, 3.4 h, and 0.17 ml·min−1. kg−1 in PM subjects and 0.22 ml·min−1·kg−1, 4.3 h and 0.15 ml·min−1·kg−1 in EM subjects. Total urinary recovery (% of dose) and ratio of hydroxy- to carboxytolbutamide were 69.4% and 0.219 respectively in PM subjects and 70.9% and 0.226 in EM subjects. There were no statistically significant differences between EM and PM metabolisers for any of these parameters. In addition there was no correlation between the debrisoquine metabolic ratio and tolbutamide urinary metabolite recovery or plasma clearance. These data indicate that hydroxylation of debrisoquine and tolbutamide are not catalyzed by the same enzyme. The ratio of hydroxy- to carboxytolbutamide in our subjects, and in other recent studies, suggests that some previous publications were inaccurate and their conclusions about the genetic control of tolbutamide metabolism were incorrect.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 152
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 579-582 
    ISSN: 1432-1041
    Schlagwort(e): budesonide ; asthma ; glucocorticoid ; pharmacokinetics ; children ; inhalation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of the glucocorticoid budesonide was studied in 6 children with asthma after i.v. injection of 0.5 mg and oral inhalation of 1 mg as an aerosol. Budesonide is a 1:1 mixture of the epimers 22 S and 22 R, which were assayed separately by HPLC combined with RIA. All pharmacokinetic parameters of the epimers differed except the half-life of about 1.5 h. It was significantly shorter than that reported in adults. Plasma clearance averaged 103 l · h−1 for epimer 22 R and 74 l · h−1 for epimer 22 S; calculated per kg body weight these values were about 50% higher than in adults. The difference was about 40% when calculated per m2 of body surface area. Since budesonide is a high-clearance drug, the data indicate higher liver blood flow · kg−1 body weight and m2 of body surface area in children. The systemic availability of the aerosol was approximately 30% of nominal dose, i.e. the same as in adults. The high clearance and short half-life of budesonide in children are advantageous in reducing the risk of possible systemic side-effects of prophylactic treatment of asthma in childhood.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 153
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 629-630 
    ISSN: 1432-1041
    Schlagwort(e): ofloxacin ; pharmacokinetics ; healthy male volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Conclusion In healthy subjects ofloxacin pharmacokinetics were found to be linear in the dose range studied (100–400 mg). The terminal half-time was 7.5–8 h and plasma ofloxacin concentrations were still detectable at 16 and 24 h after administration. The ratio of renal ofloxacin clerance: creatinine clearance was 1.35–1.82 and was not significantly different for the three doses. The non-renal clearance of ofloxacin was 40–60 ml·min−1, i.e. 20–30% of the total body clearance. Food intake delayed the absorption of ofloxacin but did not significantly modify its elimination.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 154
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1987), S. 729-731 
    ISSN: 1432-1041
    Schlagwort(e): chloroquine ; pharmacokinetics ; dose-dependence ; exponential equations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have shown that apparent nonlinearities in the pharmacokinetics of chloroquine and wide variability in reported kinetic values are possibly artefacts of experimental design. We have used simulated data based on linear equations to demonstrate that chloroquine kinetics may appear to be dose-dependent if samples are collected over a short period or if they are assayed with a method of low sensitivity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 155
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 289-295 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; pregnancy ; pharmacokinetics ; lactation ; methylxanthines ; metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of pregnancy on the disposition of theophylline were assessed in 10 patients throughout pregnancy and post-partum. The clearance relative to total theophylline concentrations was only slightly affected during the first two trimesters (2.61±0.63 l/h and 2.85±1.05 l/h), while a statistically significant reduction was evident late in pregnancy (2.05±0.49 l/h). Post-partum clearance values (2.16±2.81 l/h) suggest an ongoing suppression relative to pre-pregnancy levels. A similar pattern was evident with clearance values based on free theophylline plasma concentrations (p=0.12). Absolute volume of distribution increased in concert with gestation, suggesting that theophylline partitions into the enlarged tissue spaces. In addition, theophylline binding to plasma proteins decreased, albeit insignificantly, during the second (fraction bound=29%) and third (32%) trimesters compared to post-partum values (41%). Increases in half-life during the third trimester (13.00±2.31 h vs 9.53±3.53 h post-partum) were highly significant. This change reflects the net effect of reduced clearance and increased distribution. Breast feeding had no effect on the disposition of theophylline, although the transfer of this compound into breast milk was confirmed.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 156
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 159-164 
    ISSN: 1432-1041
    Schlagwort(e): doxepin ; cimetidine ; ranitidine ; pharmacokinetics ; biotransformation ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of cimetidine and ranitidine on doxepin pharmacokinetics was studied in 6 healthy volunteers. Each subject completed 3 study phases: Treatment A, 9 consecutive doses of 50 mg doxepin (once daily); Treatment B, same as Treatment A but co-administration of cimetidine 600 mg b.i.d. starting after the sixth doxepin dose and continuing until approximately 2 days following discontinuation of doxepin administration; Treatment C, identical to Treatment B but with ranitidine 150 mg b.i.d. instead of cimetidine. Unlike ranitidine, cimetidine co-administration resulted in a significant increase in steady state plasma levels of doxepin (4.7, 9.0 and 4.5 ng/ml during Treatments A, B and C respectively) but not desmethyldoxepin (4.1, 4.6 and 4.2 ng/ml during Treatments A, B and C respectively). Elimination half-lives of doxepin and desmethyldoxepin were prolonged by cimetidine co-administration (19.6 and 26.2 h respectively), but remained unchanged during the ranitidine treatment phase (13.3 and 18.4 h) as compared to the control phase i.e. Treatment A (13.2 and 19.0 h). These results show that cimetidine, unlike ranitidine, significantly inhibits the biotransformation of doxepin. This data has clinical implications when the co-administration of tricylic antidepressants and H2-receptor antagonists are indicated.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 157
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 191-193 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; terbutaline ; pharmacokinetics ; asthma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Theophylline and subcutaneous terbutaline are frequently used concurrently in the management of acute asthma. Recent evidence demonstrating a reduction in theophylline serum concentrations during concomitant oral terbutaline therapy prompted our evaluation of subcutaneous terbutaline's effect on theophylline pharmacokinetics. Using a randomized, placebo controlled, crossover design, the disposition of a single oral theophylline dose (7 mg/kg) was studied in eight healthy, adult males before and after repeated subcutaneous administration of terbutaline (0.25 mg). Two-way analysis of variance revealed no significant difference in elimination rate constant (ke), area under the concentration-time curve (AUC), or apparent oral clearance (CL/F) of theophylline following terbutaline administration. These results indicate that subcutaneous administration of terbutaline does not alter the pharmacokinetics of single, oral doses of theophylline in adults.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 158
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 297-301 
    ISSN: 1432-1041
    Schlagwort(e): chlorpropamide ; epileptics ; pharmacokinetics ; antiepileptic drug ; protein binding ; antipyrine test ; urine pH ; excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of liver enzyme induction and of urine pH on the pharmacokinetics of chlorpropamide have been studied. A single oral dose of chlorpropamide 250 mg was administered to 8 patients on antiepileptic drugs (phenytoin, carbamazepine) and to 8 healthy volunteers. The half-life of chlorpropamide was significantly shorter in the patients (34.4 h) than in the healthy volunteers (50.2 h), but the difference between the groups in the half-life of antipyrine was even more pronounced (5.1 vs 11.4 h). The clearance and volume of distribution of total chlorpropamide were significantly higher in the patients (2.99 ml·h−1·kg−1 and 126 ml·kg−1) than in the healthy volunteers (1.60 ml·h−1·kg−1 and 106 ml·kg−1). The unbound fraction of chlorpropamide in serum was also higher in the patients (5.7%) than in the healthy subjects (4.4%). Neither the volume of distribution nor the clearance of the free fraction of chlorpropamide differed significantly between the groups. There was a significant correlation between the half-lifes of chlorpropamide and antipyrine, and the half-life of chlorpropamide also had at least as good an inverse correlation with the urinary excretion of unchanged chlorpropamide. The renal clearance of chlorpropamide correlated well with urine pH and was almost 100-fold higher at pH 7 than at pH 5. Both the metabolic and renal clearances of chlorpropamide are important in its elimination. At urine pH higher than 6.5–7, the renal clearance of chlorpropamide represents more than half its total clearance regardless the degree of induction of liver enzymes.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 159
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 321-323 
    ISSN: 1432-1041
    Schlagwort(e): carbamazepine ; josamycin ; drug interaction ; epileptic patients ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The steady state pharmacokinetics of oral carbamazepine in epileptic patients (n=8) was compared before and after one week of treatment with josamycin (2 g/day). There was a small but statistically significant decrease in oral clearance of total (17%) and unbound (21.5%) drug. In spite of an unchanged AUC of 10,11-epoxide carbamazepine the ratio of metabolite to parent drug AUC was significantly decreased (20.2%). The plasma protein binding of carbamazepine and its 10,11-epoxide metabolite did not vary. The results demonstrate impairment by josamycin of the apparent clearance of carbamazepine. Care should be taken in patient receiving both carbamazepine and josamycin.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 160
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 619-623 
    ISSN: 1432-1041
    Schlagwort(e): indoramin ; 6-hydroxyindoramin ; bioavailability ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the pharmacokinetics and absolute systemic availability of indoramin (50 mg) given orally in solution or as a tablet with reference to intravenously administered drug (0.15 mg/kg) in 9 healthy volunteers. After intravenous administration the median apparent volume of distribution was 6.3l·kg−1, plasma clearance was 20.0 ml·min−1·kg−1, and terminal half-time was 4.1 h. When given by tablet indoramin was absorbed with moderate rapidity, with a median tmax of 1.5 h. The median systemic availability was 24%. After oral administration in solution the drug was more rapidly absorbed, with a median tmax of 1.0 h (p〈0.01). The median systemic availability was 43% (15–85%). Plasma concentrations of an active metabolite, 6-hydroxyindoramin, after single oral doses in either dosage form, were of a similar order to those of unchanged drug and fell with similar rapidity. After intravenous administration, however, concentrations of the metabolite were negligible.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 161
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 469-472 
    ISSN: 1432-1041
    Schlagwort(e): pefloxacin ; cirrhosis ; pharmacokinetics ; ascites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma and ascitic fluid concentrations of pefloxacin in 10 cirrhotic patients and 8 healthy volunteers were determined following administration of a single oral dose of 400 mg. The mean elimination half-life was significantly increased in the patients (29.0 h) compared to in 8 healthy volunteers (12.3 h). In patients, the total plasma clearance (2.71 vs 6.85 l/h) and volume of distribution (1.12 vs 1.67 l/kg) were decreased. Estimated by the ratio of the AUC in peritoneal fluid and plasma, ascitic fluid penetration was 68% after one oral dose, and pronounced accumulation of pefloxacin in ascites was found after repeated doses. Oral pefloxacin would seem to be a convenient and useful treatment of spontaneous, gram-negative, bacterial peritonitis in cirrhosis. However, the decreased hepatic metabolism of the drug leads to a marked accumulation in plasma and ascites after repeated doses, and a reduced dose is required in these patients.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 162
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 463-467 
    ISSN: 1432-1041
    Schlagwort(e): pefloxacin ; N-desmethyl-metabolite ; pharmacokinetics ; renal impairment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twenty patients (aged 26–70 years) with severely impaired renal function received pefloxacin twice daily for 5 days as 12 mg·kg−1 administered as a 1 h i.v. infusion, or 800 mg administered as tablets. On Day 5 the minimal and maximal plasma concentrations were 5.9 and 11.5 mg·l−1 respectively, after the infusion, and 8.0 and 10.4 mg·l−1, respectively, after oral administration. The steady-state level of the N-desmethyl metabolite ranged from 0.9 (infusion) to 1.2 mg·l−1 (oral route), and that of the N-oxide metabolite ranged from 6.2 (infusion) to 9.0 mg·l−1 (oral route). The minimal concentration of unchanged drug was related to the age of the patients (infusion), but the N-oxide concentration was influenced by the degree of renal impairment (both routes). The pefloxacin levels were similar to those achieved in healthy subjects, but reduced renal function leads accumulation of its biotransformation products, especially of the N-oxide metabolite which lacks antibacterial activity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 163
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 483-486 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; hyperthyroidism ; hypothyroidism ; pharmacokinetics ; clinical significance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of theophylline was investigated in five hyperthyroid, five hypothyroid, and five euthyroid patients, all with chronic obstructive pulmonary disease. Wide individual variability was found in theophylline kinetics, but the rate of elimination of theophylline was significantly higher in hyperthyroid, and lower in hypothyroid patients than in the euthyroid patients (kel=0.155, 0.060 and 0.107 h−1, respectively). The values for clearance and volume of distribution were not consistently changed compared with those in the euthyroid group, although all the parameters except AUC were significantly different in hyperthyroid and hypothyroid patients. There was a positive correlation between both thyroxine and triiodothyronine serum concentrations and total body clearance of theophylline (r=0.795 and r=0.791, respectively). It is concluded that in spite of the wide interindividual variability and the relatively small differences in the pharmacokinetics of theophylline in thyroid dysfunction compared with the euthyroid status, these differences have to be considered in certain clinical situations, as they may require changes in the therapeutic regimen for administration of theophylline in hyperthyroid or hypothyroid patients.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 164
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 511-513 
    ISSN: 1432-1041
    Schlagwort(e): carvedilol ; BM 14.190 ; pharmacokinetics ; bioavailability ; dose-linear kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and absolute bioavailability of carvedilol have been studied in 20 male healthy volunteers in a randomised 4-period, cross-over trial. Carvedilol 12,5 mg was given i.v., 50 mg was administered p.o. as a suspension and 25 and 50 mg were given in a capsule formulation. For the 50 mg capsule Cmax was 66 µg·l−1, tmax 1.2 h, t1/2 6.4 h. The t1/2 after i.v. administration was 2.4 h, CL 589 ml/min and Vz 132 l. The absolute bioavailability was 24% (50 mg capsule). The kinetics after the 25 and 50 mg capsules were consistent with dose linearity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 165
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 503-505 
    ISSN: 1432-1041
    Schlagwort(e): isosorbide-5-nitrate ; renal failure ; haemodialysis ; peritoneal dialysis ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of isosorbide-5-nitrate (IS-5-N) was studied in ten patients on haemodialysis (HD) after a single oral dose of 20 mg IS-5-N, and in six patients on continuous ambulatory peritoneal dialysis (CAPD) after repeated oral doses of 3×20 mg IS-5-N. There was significant removal of IS-5-N from blood during HD; Cmax decreased by about 20%, AUC(0–8 h) by 30% and t1/2 by about 20% from 4.3 to 3.4 h, and plasma clearance was increased by 81 ml/min. No important loss of IS-5-N was observed in patients on CAPD.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 166
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 493-498 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; erythromycin ; drug interaction ; aminophylline ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the interaction of erythromycin with theophylline. We gave ten healthy volunteers theophylline as an intravenous loading dose (5 mg·kg−1) over 1 h, followed by a maintenance infusion (0.5 mg·kg−1·h−1) for 5 h. A second infusion of theophylline was given after 9 days of treatment with 1 g erythromycin base daily, and the concentrations of theophylline were determined during the infusion periods. The concentrations of erythromycin were measured for 8 h, after one week of treatment, and also after the last erythromycin dose, simultaneously with the second theophylline infusion. Concentrations within the therapeutic range were obtained with both drugs. A significant increase in both AUC and mean plasma concentrations of theophylline was seen during erythromycin treatment. The plasma clearance of theophylline was reduced in 9 of the 10 subjects. Renal clearance increased correspondingly, but the change was not statistically significant. Serum concentrations of erythromycin fell significantly, by more than 30%, with concurrent theophylline medication. We conclude that an interaction between theophylline and erythromycin, affecting both drugs, can be shown with concentrations of the drugs within the therapeutic range.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 167
    ISSN: 1432-1041
    Schlagwort(e): nitroglycerin ; angina pectoris ; transdermal/transmucosal administration ; exercise tests ; pharmacokinetics ; Nitroderm-TTS ; Trinitrolong
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The efficacy of a transdermal (Nitroderm-TTS) and a transmucosal (Trinitrolong) nitroglycerin (NG) formulation has been compared with sublingual NG in 9 patients with ischaemic heart disease and stable angina pectoris. The duration and the degree of anti-ischaemic effect were assessed in terms of similar, individually adjusted work loads performed prior to and repeatedly after drug application in comparison with placebo. The anti-ischaemic effect of nitroderm appeared in 0.5–3 h after administration, reached a maximum in about 3.8 h and persisted for 7.9 h. The maximal nitroderm effect was significantly lower than that of sublingual NG or Trinitrolong. The effect of Trinitrolong was less variable and lasted for 4.6 h. It was evident in all patients 0.5 h after drug administration. Plasma NG levels were monitored in 9 patients after sublingual NG and trinitrolong and in 4 following Nitroderm. The relative bioavailability of Nitroderm and Trinitrolong according to the pharmacokinetic data was 29% and 256%, respectively, of sublingual NG tablets. A therapeutic NG level in blood (0.5 ng/ml) after Trinitrolong appeared much earlier (2 min) than after Nitroderm (1 h). A significant reduction in the effect of sublingual NG was observed during Nitroderm application. Thus, the transdermal NG formulation did not exhibit an antianginal effect lasting for 24 h; transmucosal NG had a relatively short, but more pronounced and stable antianginal effect.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 168
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 35-41 
    ISSN: 1432-1041
    Schlagwort(e): metronidazole ; antipyrine ; cimetidine ; phenobarbitone ; drug interaction ; drug metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of cimetidine, antipyrine and phenobarbitone on the pharmacokinetics of intravenous metronidazole and oral antipyrine has been examined in 7 healthy volunteers. The administration of cimetidine for 24 h before and throughout the sampling period failed to alter the total clearance of metronidazole or the rate of formation of the hydroxy metabolite, whereas the total and partial clearances of antipyrine were decreased 0.74 and 0.6–0.7-fold, respectively, Seven days of phenobarbitone or antipyrine administration increased the total clearance of metronidazole 1.51- and 1.86-fold, respectively, and the total antipyrine clearance was 1.22 or 1.46-fold increased, respectively. The rate of metronidazole hydroxylation was significantly enhanced by both enzyme inducers. The partial clearance of antipyrine to the normetabolite was significantly increased by both inducers, wheras the rate of 4-hydroxylation was significantly increased only by prior antipyrine administration. The results indicate that the hydroxylation of metronidazole is not inhibited by cimetidine, but that it is inducible by phenobarbitone or antipyrine. It is suggested that metronidazole and antipyrine are metabolized by different enzymatic pathways.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 169
    ISSN: 1432-1041
    Schlagwort(e): urapidil ; hypertension ; alpha-adrenoceptor blocker ; antihypertensive agent ; pharmacodynamics ; pharmacokinetics ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and haemodynamic effects of infused urapidil and an infusion-capsule combination were followed to study the correlation between the serum urapidil level and the blood pressure. Prior to urapidil administration, basal blood pressure and heart rate were measured for 16 h in 12 male hypertensive patients. Six patients received infusions lasting for 4 h of urapidil 10, 2.5 and 5 mg/h. Six patients were infused with urapidil 10 mg/h for 4 h and 2 h after the end of the infusion each took a 60-mg capsule. After a 5 day washout period the procedures were crossed over. A maximum serum urapidil level of 625±232 ng/ml was achieved at the end of the 10 mg/h infusion, when the fall in blood pressure was 37/21 mmHg. During the 2.5 and 5 mg/h infusions the serum urapidil level was 330 and 420 ng/ml, respectively, and the corresponding decreases in blood pressure were 28/16 mmHg and 31/8 mmHg. Although the urapidil concentration 1 hour after beginning the infusion was only 184±89 ng/ml a near maximal blood pressure decrease had already occurred 33±9/20±8 mmHg, whereas, 1 h after the end of the infusion the reduction in blood pressure was only 10±12/3±8 mm, with a urapidil concentration of 358±120 ng/ml. During the plateau phases of both the infusion and infusion-capsule treatments the falls in blood pressure followed the serum urapidil levels. Only in the initial rising and final falling phases of the treatments were the pharmacodynamics and pharmacokinetics of urapidil not correlated.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 170
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 93-95 
    ISSN: 1432-1041
    Schlagwort(e): tiaprofenic acid ; arthritis ; pharmacokinetics ; elderly
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the single dose and steady-state pharmacokinetic of tiaprofenic acid in ten elderly arthritic patients living in the community (5 men and 5 women) taking 200 mg tid for 8 days. The mean area under the plasma concentration-time curves to 8 h (AUC (0–8)) did not alter significantly from day 1 to day 8 (77.25 to 79.61 µg·ml−1. h). The mean terminal phase half-life (t1/2) was 2.05 h and 2.25 h on Days 1 and 8 respectively in patients in whom the calculations were possible (7 patients on Day 1 and 6 patients on Day 8). The median observed time of maximum concentration (tmax) and the mean observed maximum plasma concentration (Cmax) of 100 min and 21.3 µg·ml−1 respectively on Day 1 were not significantly different from the values obtained on Day 8 (tmax 120 min; Cmax 20.7 µg·ml−1). The kinetic data suggest that there should be no significant accumulation of tiaprofenic acid in elderly ambulant people suffering from arthritis.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 171
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 111-113 
    ISSN: 1432-1041
    Schlagwort(e): ornidazole ; neonates ; pharmacokinetics ; intravenous infusion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The single dose pharmacokinetics of ornidazole has been evaluated in 12 neonates or infants (aged 1 to 42 weeks) after the infusion of 20 mg/kg over 20 min. Plasma disposition was described by a two-compartment open model. The distribution phase was short (T1/2 (1)=0.31 h) and was followed by an elimination phase (t1/2 (2)=14.67 h). The mean apparent volume of distribution was 0.96 l/kg−1. These results did not differ from data previous by reported in adults. Total plasma clearance was between 0.4 and 1.4 ml·min−1·kg−1. The plasma concentration 24 h after the infusion was 7.32 mg·l−1, which was above the minimum inhibitory concentration for clinically significant anaerobic bacteria. Based on the pharmacokinetic results and residual concentrations at 24 h, a single daily infusion of ornidazole 20 mg·kg−1 appears adequate for therapy in neonates and infants.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 172
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 153-158 
    ISSN: 1432-1041
    Schlagwort(e): salicyl phenolic glucuronide ; rheumatoid arthritis ; aspirin ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of salicyl phenolic glucuronide (SPG) and other salicylic acid (SA) metabolites were studied at three aspirin dosage regimens in eight patients with rheumatoid arthritis. Each patient received 1, 2 and 4 g enteric coated aspirin (ASA) daily in ascending order. At the end of each 2-week dosage period, plasma and urine were collected over a dosage interval for the estimation of various pharmacokinetic parameters. With increasing ASA dosage, mean clearance of SA to SPG was approximately constant (1.8±0.3, 1.7±0.2, and 1.5±0.2 ml/min at 1, 2 and 4 g/day, respectively) when related to plasma concentrations of total SA. The percentage of the ASA dosage recovered in urine as SPG increased from 5.2±1.1 to 7.1±1.1 to 10.5±1.7 at 1, 2 and 4 g/day, respectively. It was concluded, however, that the conversion of SA to SPG is saturable, since the mean clearance of SA to SPG decreased when calculated with respect of the plasma concentration of unbound SA (13.4±1.6, 11.0±1.4, and 6.6±1.9 ml/min at 1, 2 and 4 g/day, respectively). The kinetics of the formation and excretion of salicylurate and the excretion of gentisate were similar to those found in previous studies.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 173
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 373-376 
    ISSN: 1432-1041
    Schlagwort(e): hypothermia ; fentanyl ; pharmacokinetics ; cardiopulmonary bypass ; hypothermia-induced hypoperfusion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of hypothermia on the disposition of fentanyl was evaluated in 18 children undergoing corrective cardiac surgery. They received a bolus of fentanyl followed by a continuous infusion which was stopped when cardiopulmonary bypass was established and profound hypothermia was achieved (18 °C–25 °C). Fentanyl plasma concentration remained essentially unchanged during hypothermia (6.45 ng/ml 5 min into hypothermia and 5.26 ng/ml 100–140 min later; p〉0.1). In subsequent experiments, the effect of hypothermia on the pharmacokinetics of fentanyl was studied in 4 piglets serving as their own controls. Both distribution volume (Vz) and total body clearance (CL) were significantly smaller during hypothermia. Our studies indicate that being a drug with a large distribution volume and a high hepatic extraction ratio, both CL and Vz are significantly reduced by hypothermia-induced hypoperfusion. In addition, TBC is influenced by the temperature-dependent hepatic metabolism of fentanyl.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 174
    Digitale Medien
    Digitale Medien
    Springer
    Digestive diseases and sciences 32 (1987), S. S46 
    ISSN: 1573-2568
    Schlagwort(e): pharmacokinetics ; 5-aminosalicylic acid ; chronic inflammatory bowel disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There is accumulating clinical evidence that 5-aminosalicylic acid (5-ASA), a primary metabolite of sulfasalazine (SAS), represents the therapeutic active moiety of the azo-compound SAS in the treatment of chronic inflammatory bowel disease (IBD). Since it is presumed that 5-ASA acts from the lumen of the intestine, it is important to know how much 5-ASA is released from its special galenic formulations. After liberation of 5-ASA in the terminal ileum (only slow release oral preparations of 5-ASA) and colon (5-ASA suppositories and enemas), 5-ASA is only partly absorbed. A major part of this 5-ASA is presystemically eliminated, eg, N-acetylated during its first passage through the intestinal mucosa and liver. Mean steady state plasma levels of unchanged 5-ASA are rather low (range 0.02 to 1.2 μg/ml) whereas those of Ac-5-ASA are always higher (range 0.1 to 2.9 μg/ml). This is due to the rapid elimination of 5-ASA (t1/2=0.4 to 2.4h) and the slightly slower renal excretion of the Ac-5-ASA (t1/2=6 to 9h, renal clearance=200 to 300 ml/min). The knowledge of the pharmacokinetic properties of 5-ASA from different drug formulations might contribute to a better understanding of its mode of action in IBD.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 175
    ISSN: 1573-2568
    Schlagwort(e): chronic hepatitis ; drug clearance ; pharmacokinetics ; antipyrine ; lidocaine ; aminopyrine breath test
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Chronic infection with hepatitis B virus (HBV) results in a spectrum of hepatic abnormalities ranging from minimal liver dysfunction to severe liver failure. These patients provide an opportunity to examine the relationship between the evolution of the liver disease and the ability to metabolize drugs. We have examined hepatic drug disposition in patients with chronic persistent hepatitis, chronic active hepatitis, and cirrhosis due to HBV infection. Four model drugs were used: two low-extraction capacity-limited drugs (antipyrine and aminopyrine) and two high-extraction flow-limited drugs (ICG and lidocaine). The disposition of the four drugs tested was comparable to that of healthy controls in patients with chronic persistent hepatitis, chronic active hepatitis, and mild cirrhosis. In patients with severe cirrhosis (as defined by the presence of ascites, encephalopathy, or large esophageal varices), there was a significant impairment in the aminopyrine breath test (−31%) and in the clearance of antipyrine (−53%), lidocaine (−49%), and ICG (−54%). These results indicate that impairment of drug clearance occurs only late in the evolution of HBV-related chronic liver disease. This is in keeping with the known slow and insidious progression of the disease.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 176
    ISSN: 1573-0646
    Schlagwort(e): α-difluoromethylornithine ; phase I study ; pharmacokinetics ; polyamines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Eflornithine-HCl (α-difluoromethylornithine or DFMO), an irreversible inhibitor of ornithine decarboxylase, blocks polyamine synthesis and has demonstrated antitumor activity in cell culture and animal tumor models. This phase I study was designed to determine and compare toxicity and the maximally tolerated dose of a 4-day course of DFMO given to patients in oral, continuous intravenous infusion or pulse intravenous infusion forms. Twenty-four patients were entered into this study: 8 received intravenous pulse drug, 10 intravenous continuous infusion of drug, and 6 oral DFMO. The most frequent toxicity was nausea and vomiting which occurred in 9 courses of oral drug. Only two patients receiving intravenous DFMO had nausea and vomiting. Clinically significant thrombocytopenia and audiometric abnormalities were not encountered in contrast to previous experience with 28-day courses of oral DFMO. The maximally tolerated dose of a four-day course of oral DFMO was 3.75 gm/M2 every 6 hours. The maximally tolerated dose of intravenous pulse and continuous infusion DFMO was not attained. Pharmacokinetic studies demonstrated that the intravenous schedules achieved higher plasma levels of DFMO than those previously obtained with chronic oral dosing.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 177
    Digitale Medien
    Digitale Medien
    Springer
    Investigational new drugs 5 (1987), S. 215-218 
    ISSN: 1573-0646
    Schlagwort(e): 5-methyltetrahydrohomofolate ; antimetabolite ; antifolate ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract 5-methyltetrahydrohomofolate was developed in the 1970's as an antifolate with the potential to overcome methotrexate resistance. This review summarizes the preclinical and clinical data which have accumulated to date. It is concluded that more recent, better characterized antifolates offer greater potential in achieving the goals for which this drug was introduced.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 178
    ISSN: 1573-0646
    Schlagwort(e): aclacinomycin (aclarubicin) ; pharmacokinetics ; intraperitoneal chemotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Aclacinomycin-A (Aclarubicin) is a relatively new anthracycline antibiotic with potential activity against ovarian cancer. Eight patients with various malignancies (4 ovary, 1 breast and ovary, 1 breast, 1 colon, 1 leiomyosarcoma) and intraperitoneal disease were treated in a Phase I trial with escalating doses of intraperitoneal Aclacinomycin. Drug treatments were administered through a peritoneal catheter in a 2 liter fluid volume (1.5% Dianeal). Seventeen cycles were administered with doses ranging from 25 to 75 mg of Aclacinomycin. Pharmacokinetic studies were carried out in 7 patients. Although high concentrations of Acla-cinomycin could be obtained in the peritoneal cavity no drug was detected in the plasma. The major dose-limiting toxicity was chemical peritonitis. Two patients had reduction in the amount of ascites. The recommended dose for Phase II trials is Aclacinomycin 50 mg in 2 liters given every 2 weeks.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 179
    ISSN: 1573-0646
    Schlagwort(e): ICRF-187 ; phase I ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract ICRF-187 was given to 62 evaluable patients with advanced solid tumors in a Phase I clinical trial. Weekly infusions were given in dosages ranging from 0,85 g/m2 to 7.42 g/m2 for a total of four weeks with a two week rest period between courses. Dose-limiting hematological toxicity was seen in heavily pretreated patients at a dose of 3.8 g/m2/week. All patients also developed reversible SGOT elevations. In patients with less prior therapy hematologic toxicity was not dose-limiting but hepatotoxicity, manifest by transient SGOT levels greater than 5 times baseline was seen at 7.42 g/m2/week even though only 3/6 patients could receive 4 consecutive weekly doses. At virtually all dose levels tested some patients developed anemia. Other toxicities, including alopecia, nausea, vomiting and reversible serum amylase elevations, were mild. Cumulative monthly doses achieved on this weekly schedule are significantly higher than a 48-hour infusion or daily times 3 or 5 schedule in adults and a daily times 3 schedule in children. Pharmacokinetic studies in eight patients indicate that the drug disappears from the plasma biphasically with a terminal t1/2 of 3.2 +0.9 hr. The total clearance was 288.7 + 85.0 ml/hr/kg and the volume of distribution (Vda) was 1.3 ± 0.4 1/kg. Pharmacokinetics were not dose-dependent from 3.8–7.4 g/m2 and no difference in pharmacokinetics was found in patients studied during the first and second treatments of a course. If Phase II trials of ICRF-187 are to be pursued on this schedule, appropriate doses would be 3.8 g/m2/week × 4 for heavily pretreated and 7.42 g/m2/week for “good risk” patients. Because of erratic hematologic toxicity in heavily pretreated patients, some might only tolerate three weekly doses. In good risk patients transaminitis was significant but reversible, thus, Phase II protocols should include dose escalation schemata.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 180
    Digitale Medien
    Digitale Medien
    Springer
    Investigational new drugs 5 (1987), S. 365-371 
    ISSN: 1573-0646
    Schlagwort(e): caracemide ; phase I ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A Phase I study of caracemide evaluating a short intravenous infusion repeated every 21 days is presented. Patients were entered at 85 mg/m2 with subsequent escalation levels of 170, 425, 595, and 795 mg/m2. Mild to moderate nausea and vomiting occurred at all dose levels. An apparent allergic reaction was observed at the 425 mg/m2 level. A “burning pain” originating in the mucosal areas of the head and neck, progressing to the chest and abdomen, was noted at the 425 mg/m2 level. Because of this observation, the infusion time was extended to 4 h. At the 795 mg/m2, this toxicity precluded completion of the 4 h infusion. Pharmacokinetic evaluation disclosed blood levels of 0.74–2.31 μg/ml at the 425 mg/m2 during the 0.5 h infusion. At the same dose for a 4 h infusion time, blood levels were 0.15–0.18 μg/ml. At 595 mg/m2 administered as a 4 h infusion, blood levels increased to 0.33 ± 0.14 μg/ml. The drug was cleared rapidly from the blood compartment with a half-life of 2.5 min and a total body clearance of 11.5 1/min/m2. No partial or complete response was observed. However, an advanced colon carcinoma patient experienced subjective pain relief with a decrease in carcinoembryonic antigen. The dose-limiting toxicity of caracemide using the 4 h infusion was an intolerable “burning pain” with a maximum tolerated dose of 795 mg/m2. Further characterization of this dose-limiting toxicity is required prior to further clinical evaluation of caracemide.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 181
    ISSN: 1573-8221
    Schlagwort(e): prazosin ; prazosin metabolite ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 182
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 103 (1987), S. 658-660 
    ISSN: 1573-8221
    Schlagwort(e): ethanol ; rats ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 183
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 104 (1987), S. 941-944 
    ISSN: 1573-8221
    Schlagwort(e): ethanol ; predisposition ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 184
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 15 (1987), S. 145-177 
    ISSN: 1573-8744
    Schlagwort(e): Chemotherapy ; mutation ; resistance ; compartmental analysis ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The pharmacokinetics of antineoplastic drugs based on compartmental models are combined with deterministic exponential growth models of tumors containing drug-resistant and sensitive cells. Model predictions for single-drug therapy are compared with in vivodata obtained by other investigators for L1210 t-cell leukemia in mice treated with BCNU and AraC and for in vitrotreatment of L1210 with Ara-C. The model and data compare favorably in terms of rate of tumor growth and duration of drug action for both constant infusion and bolus delivery of the drugs.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 185
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 15 (1987), S. 5-13 
    ISSN: 1573-8744
    Schlagwort(e): Structure-activity relationships ; pharmacokinetics ; protein binding ; glycopeptide antibiotics ; charge ; lipophilicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract In previous studies of the pharmacokinetics and urinary excretion of nine glycopeptides with diverse isoelectric points (pI),as pIdecreases, the total systemic and renal clearance, urinary recovery, and volume of distribution decrease, whereas the half-life increases. With glycopeptides of similar pI,clearance decreases and half-life increases with increasing lipophilicity. The present study examines the serum protein binding of these glycopeptide antibiotics in mouse, rat, and human serum and calculates the previously reported pharmacokinetic parameters for these drugs based on unbound concentration. Increased negative charge and lipophilicity increase serum protein binding (90-fold, fu 83% to 0.96%), which decreases the renal clearance and total systemic clearance (90-fold, 16.4 to 0.18 ml/min/kg) of these drugs. Increased serum protein binding also decreases the volume of distribution of these compounds, but this change is relatively small (sixfold, 755 to 131 ml/kg) compared with the change in total systemic clearance causing an increase in elimination half-life (25-fold, 20 to 492 min). The results demonstrate that the large differences in the total systemic clearance and half-life of these glycopeptide antibiotics are primarily due to dramatic differences in serum protein binding and notto differences in the intrinsic elimination processes (enzymes or transport proteins). It appears that the same physical-chemical properties that govern the protein binding and pharmacokinetics of small organic molecules govern the disposition of these high-molecular weight glycopeptide antibiotics.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 186
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 15 (1987), S. 255-269 
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; singie-point dose prediction ; dosage ; minimax estimation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The single-point dose prediction method is based on the observation that for drugs obeying single compartment elimination kinetics there is a nearly constant reciprocal relation between the plasma level at a fixed time following a single loading dose and the dose that is required to maintain the desired steady state plasma level of the drug. This paper describes an improved method for choosing a plasma sampling time and a proportionality constant. It applies to either drugs administered intravenously or to drugs whose rates of absorption from the site of administration are very rapid compared to their rates of elimination from the body. The sampling time and proportionality constant chosen are those that minimize the maximum relative deviation of the maintenance dose estimated by the single-point method from the dose that would be estimated if the individual's true elimination rate constant were known. The paper also supplies a method to determine the maximum error that may be introduced into the estimation of the maintenance dose by using the single-point method.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 187
    ISSN: 1573-8744
    Schlagwort(e): cotinine ; nicotine ; rat ; tissue distribution ; pharmacokinetics ; constant-rate infusion ; physiological model ; iv bolus ; osmotic minipump
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The tissue partition of cotinine was measured by a GC-MS method following a 6-day constant-rate input of nicotine and cotinine to male rats by means of an osmotic minipump. The tissue-to-blood partition coefficients of cotinine were calculated for adipose (0.08), brain (0.48), heart muscle (0.55), intestinal (0.53), hepatic (0.64), pulmonary (0.50), renal (0.99), and skeletal muscle tissue (0.51), following the cotinine infusion. When nicotine was infused the tissue partitioning of cotinine increased by a factor of 2.3–4.9, depending on the tissue sampled. Another group of animals were killed at timed intervals from 10 min to 30 hr, after having received a single intravenous bolus dose of 0.5 mg cotinine, and the washout of cotinine was traced in blood and tissues. A physiological model was used to simulate the disposition of cotinine. Generally, the model-predicted concentrations were consistent with those found experimentally. The fractional uptake of cotinine into various tissues was simulated. Blood, intestinal, and skeletal muscle tissues embodied more than 70% of the total body load of the drug. Clearance (Cl),volume of distribution (Vd),and the biological half-life (t1/2)were calculated both from the infusion study and by fitting a monoexponential model to the iv blood data of the rat. Significant differences were found in the apparent clearance calculated from the single iv bolus dose compared to the constant rate infusion. The volume of distribution was, however, consistent from both studies. The impact of a change in clearance was also simulated.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 188
    ISSN: 1573-8744
    Schlagwort(e): veralipride ; pharmacokinetics ; enterohepatic recycling ; double site of drug absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Equal doses of veralipride have been given to 12 healthy volunteers by three different administrations-intravenous infusion, oral solution, and oral capsule-in a randomized cross-over design. After the intake of the solution, but not after infusion or capsules, two maximum plasma concentrations have been observed and interpreted, according to a double-site model for drug absorption.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 189
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 15 (1987), S. 39-55 
    ISSN: 1573-8744
    Schlagwort(e): Ajmaline ; antiarrhythmic drug ; pharmacokinetics ; pharmacodynamics ; plasma protein binding ; combined pharmacokinetic-pharmacodynamic model ; ECG
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Pharmacokinetics and pharmacodynamics of ajmaline were studied in four healthy dogs after intravenous administration of the drug at the infusion rate of 1.0 mg/min for 45 min. Ajmaline exhibited a saturable binding to plasma protein. One kind of binding site was found in the range of observed drug concentrations and its binding capacity showed nearly threefold interindividual difference. The time course of ajmaline concentration in whole blood Cbcould be described by the two-compartment open model and the unbound concentration of ajmaline in plasma Pf wasestimated from Cbby using the hematocrit value and the parameters of plasma protein binding and erythrocyte partitioning. The pharmacologic responses to ajmaline were assessed by recording ECG, and the changes in PQ and QRS interval were studied in relation to ajmaline disposition. When ECG changes were related to the ajmaline concentration, a significant degree of hysteresis was observed. The relationship between the unbound drug concentration and the pharmacologic effect was analyzed by a combined pharmacokinetic-pharmacodynamic model, where the hypothetical effect compartment is connected to the Pfin the central compartment by a first-order process. This model allows estimation of the changes in PQ and QRS intervals after intravenous administration of ajmaline. By comparing the drug effect on PQ and QRS intervals, it was suggested that ajmaline distributes to the atrial and the ventricular tissue in a similar degree and causes a reduction in the conduction rate in both sites with similar activity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 190
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 15 (1987), S. 101-115 
    ISSN: 1573-8744
    Schlagwort(e): Lignocaine ; MEGX ; pharmacokinetics ; pharmacodynamics ; active metabolite
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Lignocaine clearance declines during continuous intravenous infustion in man and in vitrostudies suggest that this may partly be due to inhibition by MEGX, a metabolite of lignocaine, MEGX is pharmacologically active in animals, but this is not yet proven in man. This study examined the pharmacokinetics and pharmacodynamics of lignocaine and MEGX in eight healthy male volunteers given lignocaine HCl 120mg, MEGX HCl 120 mg, lignocaine HCl 120 mg+MEGX HCl 120 mg, and placebo, administered according to a randomized double-blind protocol. One-, two-, or three-compartment models were fitted to drug and metabolite blood concentration-time profiles and clearance, volume (V ss ), andhalf-life values were calculated and compared by paired t-test. Systolic time intervals and QTinterval were recorded and compared by repeated measures ANOVA. When administered in combination with MEGX, lignocaine clearance was significantly reduced from 58±18 to 48±13 L hr(su−1) (p 〈0.02). The V(inss) was unchanged and there was a trend toward an increase in terminal half-life. Lignocaine, MEGX, and the combination significantly reduced QTinterval up to 30 min after injection and this was maintained to 2 hr with the lignocaine and the combination. Transient side effects were experienced with all active treatments, but were most pronounced with the combination. Thus, lignocaine clearance was inhibited by MEGX, which was pharmacologically active in man.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 191
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 15 (1987), S. 557-568 
    ISSN: 1573-8744
    Schlagwort(e): etintidine ; propranolol ; 4-hydroxypropranolol ; interaction ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Etintidine HCl is a potent H2 -blocker. The effect of clinical doses of etintidine on the disposition of a single oral dose of propranolol was investigated in 12 normal subjects. This was a double-blind, two-way crossover study. Each subject received etintidine (400 mg) or placebo twice a day with meals for 4 days on two occasions (separated by 4 days). On each occasion, the subjects were fasted overnight on Day 3 and were given an oral dose of Inderal® (40 mg propranolol hydrochloride) 30 min following the administration of the morning dose of etintidine or placebo on Day 4. Blood samples were collected prior to and up to 24 hr following the administration of propranolol. The plasma samples were analyzed for propranolol and 4-hydroxypropranolol by HPLC. Comparison of the pharmacokinetic parameters of propranolol between etintidine and the placebo groups indicates that etintidine significantly increased the AUC0−∞,values (573.5 vs. 146.4 ng·hr/ml, p=0.0001)and prolonged the elimination half-life (4.61 vs. 2.33 hr) of propranolol. Statistical evaluation of the pharmacokinetic parameters of 4-hydroxypropanolol indicates that etintidine also increased the AUC0−24 values (43.8 vs. 16.4 ng·hr/ml, p=0.0028) and prolonged the elimination half-life (4.87 vs. 1.97 hr) of 4-hydroxypropranolol. The data suggest that etintidine, like cimetidine, impaired the elimination of propranolol. Etintidine also protracted the elimination of 4-hydroxypropranolol, an active metabolite of propranolol.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 192
    ISSN: 1573-904X
    Schlagwort(e): etretinate ; pharmacokinetics ; dose proportionality
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Twelve healthy male subjects received single oral doses of etretinate, ranging from 25 to 100 mg (1 to 4 × 25-mg capsules) in an open-label, four-way randomized crossover design. Plasma concentrations of etretinate and two active metabolites were determined by a specific high-performance liquid chromatographic (HPLC) method. Analysis of variance and orthogonal contrasts were used to assess dose proportionality. Mean (± %CV) maximum concentrations after 25- to 100-mg doses were 133 (50), 195 (33), 261 (53), and 446 (65) ng/ml, whereas AUC0−12 values were 581 (46), 1090 (39), 1500 (52), and 2440 (63) ng · hr/ml, respectively. The test for proportionality indicated that C max and AUC0−12 increased proportionally with an increase in dose (P 〉 0.05).
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 193
    ISSN: 1573-904X
    Schlagwort(e): oral cephalosporin ; cefixime ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Cefixime (CL 284,635; FK 027) is a new third-generation oral cephalosporin. To study dose-dependent pharmacokinetics of cefixime in dogs, two balanced four-way crossover studies were conducted. In the first study, oral doses of 50, 100, and 200 mg/kg and an intravenous dose of 50 mg/kg cefixime were administered. In the second study, oral doses of 6.25, 12.5, and 25 mg/kg and an intravenous dose of 12.5 mg/kg cefixime were administered to the same dogs. A period of 1 month separated the two studies. When the two intravenous doses were compared (i.e., 12.5 and 50 mg/kg), a twofold increase in clearance and volume of distribution was observed after the higher dose. The oral systemic bioavailability in the dose range 6.25–50 mg/kg was 55%. It decreased to 44% at 100 mg/kg and 27% at 200 mg/kg. The average peak serum concentrations ranged from 15.8 µg/ml at 6.25 mg/kg to 119 µg/ml at 200 mg/kg. Within this concentration range, the fraction of free drug in serum (unbound to proteins) increased from 7 to 25%. This concentration-dependent protein binding was primarily responsible for changes in total clearance, volume of distribution, and bioavailability of the drug in dogs.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 194
    ISSN: 1573-904X
    Schlagwort(e): enterohepatic recirculation ; pharmacokinetics ; bioavailability ; area under the curve ; bile ; hepatic extraction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A relationship between systemic availability and its determinants has been derived for a physiologically realistic model of drug disposition that includes enterohepatic cycling (EHC), gallbladder emptying (with an arbitrary time course), first-pass metabolism to noncycling metabolites, and fecal excretion. Systemic availability (F) has been shown to be determined by the fraction of the dose initially absorbed (f a*), the fraction of the drug excreted into the GI tract that is reabsorbed with each cycle (f a), the hepatic extraction ratio (E), and the fraction of extracted drug that is transported to the gallbladder for EHC (f g) according to the relationship F = f a*(1 −E/(1 − f a f g E) The implications of the above relationship are that (1) systemic availability is dependent on EHC, (2) values of F calculated to be greater than unity cannot be explained simply by the presence of EHC, (3) calculations of E based on the usual expression F = f a* (1 − E) are erroneous for drugs subject to EHC, and (4) a compound that has a high systemic availability and is subject to EHC is not necessarily inefficiently metabolized. The quantitative interrelationship of systemic availability and its determinants is illustrated using a contour plot. Slices through the surface are used to demonstrate that the presence of EHC changes the sensitivity of F to changes in E.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 195
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 4 (1987), S. 59-61 
    ISSN: 1573-904X
    Schlagwort(e): mean residence time ; pharmacokinetics ; Michaelis–Menten elimination ; one-compartment model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract An equation for the mean residence time (MRT) of drug in the body is derived for the system where drug is injected intravenously into a one-compartment model and eliminated by a single, capacity-limited process. This MRT is a complex function of dose, volume, V m, and K m but degenerates into the classical volume/clearance expression under limiting low-dose conditions (K m ≫ C 0). The equation was validated by comparison of the MRT obtained by direct calculation versus numerical area estimation for simulated data. The equation may be useful analytically in the estimation of the fundamental Michaelis–Menten parameters, V m and K m, from experimental data.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 196
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 4 (1987), S. 251-254 
    ISSN: 1573-904X
    Schlagwort(e): amiodarone ; antipyrine ; desethylamiodarone ; drug metabolism ; drug interactions ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The effect of amiodarone on hepatic drug metabolism in vivo was examined in the rat using antipyrine as a model substrate. Pretreatment with oral amiodarone hydrochloride, 100 mg/kg/day, for 5 days resulted in a 19% reduction in antipyrine clearance and a 22% increase in half-life. The administration of single oral doses of amiodarone hydrochloride, 100 mg/kg, 1 or 5 hr prior to antipyrine administration had no significant effect on antipyrine pharmacokinetics. The administration of a single intravenous dose of amiodarone hydrochloride, 50 mg/kg, reduced antipyrine clearance by 32% and increased the half-life by 46%. The desethyl metabolite of amiodarone was also found to reduce antipyrine clearance (21%) after a single oral dose of 100 mg/kg.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 197
    ISSN: 1573-904X
    Schlagwort(e): computer-designed formulation ; prolonged-action dosage forms ; drug delivery systems ; long-acting formulations ; theophylline delivery systems ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The method provides an a priori assessment of the maximum allowable flexibility in the rate of release from a prolonged-release formulation. The clinical pharmacokinetic parameters describing the drug candidate are employed to calculate the ranges of rate constants and doses required for the formulation to provide a selected therapeutic duration. For a given patient, there may be an infinite number of combinations of release rate constants and dose sizes which will maintain steady-state plasma drug concentrations within a desired range when the formulation is administered at the selected dosing interval. Computer simulations of steady-state plasma concentrations are employed to establish the ranges for all of the acceptable rate constants and doses for each member of a group. The entire group is then examined to define the range of release rate constants and doses which would provide a useful formulation for every member in the group. Literature values for theophylline clinical pharmacokinetics in children and adults have been employed to illustrate the application of this method. The method is unique in that it provides an entire range of release rates on which to gauge the feasibility for success.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 198
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 4 (1987), S. 332-336 
    ISSN: 1573-904X
    Schlagwort(e): pharmacokinetics ; gold ; rabbits ; intramuscular ; intravenous ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Male, New Zealand white rabbits (3.5–4.3 kg) received a single 2-mg/kg dose of gold sodium thiomalate (Myochrysine) via intramuscular (N = 4) and intravenous (N = 3) routes. Blood samples were drawn from the marginal ear vein for a period of 5–10 days. The concentration of gold in whole blood was determined using graphite furnace atomic absorption spectrophotometry. The blood concentration–time profiles obtained following both routes of administration were best described by a two-compartment open model with first-order absorption for the intramuscular route. Gold was absorbed rapidly with a mean (harmonic) absorption half-life of 9.0 min, with a peak concentration of 6.0 ± 1.0 µg/ml (N = 4). Blood concentrations declined in a biphasic manner; the mean α half-lives were 0.738 and 1.78 hr for the iv and im routes, respectively. The corresponding terminal (β) half-lives were 54.1 and 63.0 hr. The estimated volume of the central compartment (70 to 93 ml/kg) agreed closely with the rabbit blood volume. The mean ( ±SD) extent of the dose absorbed following intramuscular injection was 68.9 ± 12.4%.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 199
    ISSN: 1573-904X
    Schlagwort(e): zero-order delivery ; drug delivery system ; sustained release ; computer simulation ; dosage form design ; theophylline ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Classical methods employing pharmacokinetic data to calculate zero-order release rates for sustained release products require that a constant-rate drug delivery system must have a duration which is exactly equal to the desired dosage interval. This traditional approach fails to establish the minimum acceptable duration and also fails to provide any flexibility in the formulation goal. While it does calculate one pair of duration and dose values, there are infinite pairs of values capable of maintaining the desired plasma concentrations using the selected dosing interval. In the current method, computer simulations are used to establish the boundary conditions within which any pair of duration and dose values will maintain the desired levels when administered on the chosen dosing interval. By comparing the boundary conditions for every subject in a group, a single set of conditions which would work for the entire group can be selected. These final limits represent the broadest specifications for zero-order drug delivery system design for that particular drug combined with the plasma concentration goals and the desired dosing interval. The method is illustrated using theophylline pharmacokinetics.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 200
    ISSN: 1573-7241
    Schlagwort(e): drug interactions ; digoxin ; pharmacokinetics ; antiarrhythmic drugs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary While preliminary screening for interactions between new cardiovascular pharmacotherapeutic agents and digoxin can be efficiently and safely conducted in normal healthy volunteers, it is particularly important to detect and quantify drug interactions in patients with varying degrees of cardiac, hepatic and/or renal dysfunction. Much of the previously published literature provides only minimal data to guide clinical practice because of limitations of study design including sample size and measurement techniques. Important factors that determine the ability of a particular study design to detect a drug interaction with digoxin include the accuracy and precision of the assay method for serum digoxin concentrations, intrasubject and intersubject variability in serum digoxin concentration, and sample size. The format of the trial (chronic versus single digoxin dosing in cardiac patients; chronic verus single digoxin dosing in normal subjects) and the method of assessment of alterations in digoxin handling (formal determination of digoxin clearance, comparison of multiple or single digoxin measurements during various phases of trial) also impact greatly on the clinical relevance of such investigations. Guidelines for future studies of drug interactions with digoxin in cardiac patients are proposed with particular emphasis on laboratory methods; measurement techniques during baseline, placebo, and active drug phases; calculation of the statistical power of the study; time course of the trial; and assessment of the clinical significance of the findings.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
Schließen ⊗
Diese Webseite nutzt Cookies und das Analyse-Tool Matomo. Weitere Informationen finden Sie hier...