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  • Electronic Resource  (125)
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  • 1990-1994  (125)
  • 1990  (125)
  • pharmacokinetics  (125)
  • 1
    Electronic Resource
    Electronic Resource
    Effect of ponsinomycin on cyclosporin pharmacokinetics (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 165-167 
    Details
    ISSN: 1432-1041
    Keywords: Cyclosporin A ; ponsinomycin ; pharmacokinetics ; drug interaction ; macrolide antibiotic ; renal transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of treatment with ponsinomycin, a new macrolide antibiotic, on the pharmacokinetics of cyclosporin A has been studied in 10 renal transplant patients. The pharmacokinetics of cyclosporin A was investigated at steady state, before and during treatment with ponsinomycin. On average, the blood levels of cyclosporin A were doubled by the macrolide, possibly due to a decrease in elimination or/and to an increase in absorption. Ponsinomycin should be use very carefully in patients treated with cyclosporin A.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280052
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of age on single- and multiple-dose pharmacokinetics of erythromycin (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 161-164 
    Details
    ISSN: 1432-1041
    Keywords: erythromycin ; pharmacokinetics ; steady-state ; elderly subjects ; age effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of age on the pharmacokinetics of erythromycin was investigated by comparing its kinetic behaviour in eight young healthy adults and eight healthy elderly subjects after single and repeated oral doses of erythromycin stearate 1 g b.d. for 7 doses. The peak serum concentration and area under the serum concentration-time curve (AUC) were significantly greater in the elderly subjects than in the young controls after single and multiple doses. Accordingly, the apparent oral clearance was lower in the elderly subjects (0.31 vs 0.64 and 0.22 vs 0.69 l·h−1·kg−1 after the first and seventh administration, respectively). The mean elimination half-life was significantly longer in the elderly group only after multiple dosing (4.8 vs 2.3 h). No age-related difference was observed in the time to peak serum concentration and apparent volume of distribution. The multiple-dose regimen resulted in an almost two-fold accumulation of erythromycin in the older individuals and no accumulation in the young adults. Mean drug accumulation in elderly subjects at steady state was 43% greater than was predicted from the AUC after the first dose, suggesting a time-dependent reduction in both systemic and presystemic clearance. The results indicate that the metabolic elimination processes for erythromycin are impaired in normal elderly subjects and suggest that caution is required on administering a high dose of it to aged people.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280051
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  • 3
    Electronic Resource
    Electronic Resource
    A randomized double-blind study of bisoprolol versus atenolol in mild to moderate essential hypertension (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 21-24 
    Details
    ISSN: 1432-1041
    Keywords: bisoprolol ; atenolol ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have compared the efficacy and pharmacokinetics of bisoprolol, a new cardioselective beta-adrenoceptor antagonist, with atenolol in a randomized double-blind crossover study in 12 patients (mean age 53.5 y) with mild to moderate essential hypertension. After a two week placebo wash-out period without any antihypertensive therapy, the patients were given bisoprolol 10 mg daily or atenolol 50 mg daily, increasing to 20 mg or 100 mg respectively if the sitting diastolic blood pressure did not fall below 90 mm Hg after two weeks of therapy. Crossover occurred after six weeks of active therapy followed by two weeks of placebo wash-out. After 6 weeks of therapy both drugs significantly reduced sitting and standing diastolic blood pressures (bisoprolol by 15% and 16% respectively, atenolo by 11% in both cases). However, while sitting and standing systolic pressures were significantly reduced by bisoprolol (13% and 16% respectively), only standing systolic pressures were significantly reduced by atenolol (11%), and this reduction was significantly less than with bisoprolol (p〈0.05). Both drugs similarly reduced mean sitting and standing heart rates. There were no significant differences between the single-dose and steady-state kinetics of either bisoprolol or atenolol. The mean plasma elimination half-life (t1/2) increased from 12.9 to 13.2 h during steady state on bisoprolol and from 7.2 to 11.5 h on atenolol. The apparent volume of distribution (Vz) was greater for bisoprolol than for atenolol after single dosing (235 1 vs 146 1) and at steady state (216 1 vs 137 1), but clearances were similar for both drugs. The maximum plasma concentration (Cmax) of bisoprolol increased from 45 μg·l−1 to 72 μg·l−1 during steady state and the Cmax of atenolol increased from 321 μg·l−1 to 410 μg·l−1 Adverse effects occurred in only one patient (lethargy while taking atenolol). These results suggest that bisoprolol has similar efficacy, safety, and pharmacokinetics to atenolol in patients with mild to moderate essential hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314797
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  • 4
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of cotinine in plasma and saliva from non-smoking healthy volunteers (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 281-287 
    Details
    ISSN: 1432-1041
    Keywords: Cotinine ; non-smokers ; saliva levels ; plasma levels ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cotinine is a major metabolite of nicotine in man. Its disposition kinetics has been followed in plasma and saliva from nine nonsmokers, 23 to 56 years of age. Cotinine 5, 10 and 20 mg was given intravenously and orally to each subject, and plasma, saliva and urine samples were collected for 96 h. The kinetics of cotinine was best described by a multi-compartment model with three distinct phases both in plasma and saliva. Regardless of the mode of administration, there was no indication of dose-dependent kinetics. Mean total plasma clearance was 63.8 ml·h−1·kg−1 and mean renal clearance was 4.7 ml·h−1·kg−1, i.e. only 10% of the dose was excreted unchanged in the urine. The volume of distribution, as calculated from the plasma curves, was slightly greater than the body weight, 1.1 l·kg−1. The concentration of cotinine was 20 to 40% higher in unstimulated mixed saliva than in plasma during the absorption, distribution and elimination phases. As the clearance and distribution values in saliva were directly proportional to the corresponding values in plasma, similar terminal half-life values were obtained in the two body fluids, 15.5 and 16.8 h for plasma and saliva, respectively. Thus the kinetics of cotinine is linear after intravenous and after oral dosing, and salivary concentrations give the same information about cotinine disposition in the body as do plasma concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315031
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  • 5
    Electronic Resource
    Electronic Resource
    Removal of famotidine by haemodialysis in elderly anuric patients (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 313-314 
    Details
    ISSN: 1432-1041
    Keywords: famotidine ; anuric patients ; haemodialysis ; H2-receptor antagonist ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of haemodialysis on the pharmacokinetics of oral famotidine has been studied in five elderly anuric patients. Famotidine 20 mg was administered in a cross-over design to patients on and not on haemodialysis. The elimination rate constant of haemodialysis (k) was 4.6-fold larger than the systemic elimination rate constant (ke). Although the mean maximum serum concentration of famotidine during haemodialysis (141.5 ng·ml−1) was not significantly lower than that without haemodialysis (195.6 ng·ml−1), the AUC up to 5 h during haemodialysis was significantly decreased to 58.1% of the value without it. The data suggest that famotidine is dialysable by haemodialysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315039
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and metabolism of iodo-doxorubicin and doxorubicin in humans (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 507-513 
    Details
    ISSN: 1432-1041
    Keywords: Anthracyclines ; cancer patients ; iodo-doxorubicin ; doxorubicin ; pharmacokinetics ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of doxorubicin (DOX), iodo-doxorubicin (I-DOX) and their metabolites in plasma has been examined in five patients each receiving 50 mg/m2 of both anthracyclines as a bolus injection. Terminal half-life, mean residence time (MRT), peak plasma concentration Cmax, and area under the curve (AUC) appeared smaller for I-DOX, whereas its plasma clearance (CLp) and volume of distribution at steady state (Vss) were larger than for DOX. The major metabolite of I-DOX was iodo-doxorubicinol (I-AOL) followed by doxorubicinol aglycone (AOLON). The AUC of I-AOL was 6-times larger than that of its counterpart AOL, which is the major metabolite of DOX. AOLON generated after I-DOX administration is a further important metabolite, as its AUC was 10-times larger than that of AOLON generated from DOX. The other aglycones, such as doxorubicin aglycone (AON) and the 7-deoxy-aglycones were only minor metabolites after either I-DOX or DOX injection. The ratio AUCI-AOL/AOL/AUCI-DOX/DOX was 27 in the case of I-DOX and 0.4 after DOX. The terminal half-lives of the cytostatic metabolites I-AOL and AOL were similar, although a longer MRT for AOL was calculated. Both metabolites had much longer MRTs than their parent drugs. The MRTs of the aglycones AOLON and AON were greater than those of the 7-deoxy-aglycones after both I-DOX and DOX. Approximately 6% DOX and less than 1% I-DOX were excreted by the kidneys during the initial 48 h. About 5% of I-DOX was excreted via the kidneys as I-AOL. Aglycones were not detected in significant amounts. The plasma concentrations of all compounds measured were highest during the first few minutes after administration of I-DOX and DOX. The I-AOL concentration was comparable to that of I-DOX immediately after the injection, due to very rapid metabolism within the central compartment (vascular space) by the aldoketo reductase system in the erythrocytes. The plasma concentration-time curves of (7d)-aglycones showed a second peak between 2 and 9 h after injection, suggesting enterohepatic circulation of metabolites lacking the daunosamine sugar moiety.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280945
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  • 7
    Electronic Resource
    Electronic Resource
    Indirect assessment of the enterohepatic recirculation of piroxicam and tenoxicam (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 547-549 
    Details
    ISSN: 1432-1041
    Keywords: piroxicam ; tenoxicam ; cholestyramine ; pharmacokinetics ; enterohepatic circulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess the extent of enterohepatic recycling of piroxicam and tenoxicam, their pharmacokinetics have been compared in the absence and presence of concomitant treatment with cholestyramine. In a randomized crossover study 6 healthy volunteers received piroxicam and tenoxicam 20 mg p.o., alone or with cholestyramine 24 g/day for 4 days. Cholestyramine increased piroxicam & tenoxicam elimination approximately 2-fold (t1/2 50.3 vs 28.1 h and 73.6 vs 35.8 h, respectively). It also increased the apparent clearance (Cl/f) of piroxicam and tenoxicam by 58% and 112%. When cholestyramine was administered, the t1/2 of piroxicam & tenoxicam were correlated (r=0.89), which suggests that their hepatic biotransformation is under a common control. It is concluded that: piroxicam and tenoxicam are eliminated to a large and comparable extent through the biliary route, and the administration of cholestyramine may help to accelerate their elimination in cases of overdosage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278579
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of isradipine in patients with chronic liver disease (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 599-603 
    Details
    ISSN: 1432-1041
    Keywords: Isradipine ; cirrhosis ; systemic ; calcium antagonist ; aminopyrine breath test ; serum bile acids ; galactose elimination ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the dihydropyridine calcium antagonist isradipine has been examined in 8 healthy volunteers, 7 patients with non-cirrhotic chronic liver disease (CLD), and 8 patients with biopsy-proven cirrhosis (CIR). Isradipine was simultaneously given orally (12C 5 mg) and i.v. (13C 1 mg). Systemic availability was significantly increased from 17% and 16% in controls and CLD, respectively, to 37% in CIR. The corresponding systemic clearances averaged 1.1, 0.9 and 0.61 · min−1, the reduction in cirrhotics being significant. Both aminopyrine demethylation capcity, a measure of hepatic microsomal function, and indocyanine green disappearance, a measure of hepatic perfusion, were correlated with the reduction in systemic clearance, and the reduction in oral clearance was correlated with the reciprocal of the serum bile acid concentration. The loss of first-pass extraction should be considered when this calcium antagonist is given perorally in patients with hepatic cirrhosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278589
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  • 9
    Electronic Resource
    Electronic Resource
    Absorption kinetics of oral and rectal flecainide in healthy subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 595-598 
    Details
    ISSN: 1432-1041
    Keywords: flecainide ; pharmacokinetics ; absorption ; non-parenteral administration ; healthy subjects ; rectal administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption kinetics of different pharmaceutical formulations of orally and rectally administered flecainide have been assessed in a cross-over study in 7 healthy volunteers. The subjects received single doses of flecainide after a washout period of at least one week. A tablet, an oral solution, a rectal solution and a 10 min i.v. infusion during 10 min each containing 100 mg flecainide were administered to the subjects in a randomized order. The mean absolute bioavailability was 98%, 78% and 81% for the rectal and oral solutions and the tablet. The lag time after administration of the oral solution was 0.33 h and it was 0.86 h after the tablet and 0.18 h after the rectal solution. The mean time to the peak serum concentration (tmax) after the rectal solution (0.67 h) was shorter than after either the tablet (4 h) or oral solution (1 h). The maximum serum concentration (Cmax) was 0.29 mg · 1−1 after the rectal solution, 0.14 mg · 1−1 after the tablet and 0.17 mg · 1−1 after the oral solution. All the volunteers showed significantly higher serum flecainide concentrations during the first 20 min of the absorption phase after rectal administration of 100 mg flecainide as a solution compared to its oral administration. In conclusion: based on the absolute bioavailability, Cmax, tmax, and lag times, rectal administration of flecainide solution gave a better absorption profile than after oral tablet or solution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278588
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  • 10
    Electronic Resource
    Electronic Resource
    Albendazole kinetics in patients with echinococcosis: Delayed absorption and impaired elimination in cholestasis (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 605-608 
    Details
    ISSN: 1432-1041
    Keywords: albendazole ; albendazole sulphoxide ; absorption ; elimination ; benzimidazole ; pharmacokinetics ; echinococcosis ; cholestasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of albendazole and its main metabolite, albendazole sulphoxide, have been examined after giving a single oral dose of 200 mg albendazole to 19 patients with either Echinococcus multilocularis or E. granulosus, 5 of whom had significant extrahepatic obstruction due to the underlying disease. The AUC of albendazole sulphoxide was increased in the latter patients (mean 122 μmol · h · l−1 compared to 17 μmol · h · l−1 in the non-obstructed group). Obstructed patients had delayed absorption, ka averaging 0.39 compared to 1.41 h−1 in non-obstructed patients. The corresponding elimination rate constant, ke was also prolonged, averaging 0.041 and 0.13 h−1 in the two groups, respectively. Four patients were restudied after complete or partial resolution of the cholestasis. The pharmacokinetic parameters in them had returned towards values comparable to those in the non-obstructed patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278590
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  • 11
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and endocrine effects of terguride in healthy subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 609-615 
    Details
    ISSN: 1432-1041
    Keywords: Terguride ; partial dopamine agonist ; pharmacokinetics ; endocrine effects ; pituitary hormones ; 6β-OH cortisol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of the partial dopamine agonist, terguride, were measured by RIA in healthy volunteers after a single i. v. dose of 50 μg and on the first and seventh day of an oral treatment with 250 μg, 500 μg and 750 μg b. d. Basal and releasing hormone (TRH, GHRH, CRF, LHRH) — stimulated pituitary hormone secretion (PRL, TSH, GH, FSH, LH) and cortisol were also determined by RIA. Following the i. v. injection, plasma terguride levels declined biphasically, with half-lives of 0.2 and 1.5 h; total clearance was 17 ml·min−1·kg−1. the oral bioavailability of terguride over all doses was about 20%. Basal and TRH-stimulated prolactin levels were dose-dependently depressed, but the secretion of other hormones remained unaffected. Tolerance of terguride was excellent and there was no negative effect on performance or mood, nor on mixed-function oxygenase activity, assessed as urinary 6β-OH cortisol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278591
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  • 12
    Electronic Resource
    Electronic Resource
    Influence of midazolam on the plasma concentrations of mepivacaine after lumbar epidural injection in children (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 91-92 
    Details
    ISSN: 1432-1041
    Keywords: Midazolam ; Mepivacaine ; local anaesthetic ; lumbar epidural anesthesia ; children ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty children undergoing surgery received a lumbar block using 0.4 ml/kg mepivacaine 2.0%. They were randomized into two groups, one of which received midazolam 0.4 mg/kg rectally as premedication. Midazolam administration did not significantly influence the plasma concentrations of mepivacaine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314812
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  • 13
    Electronic Resource
    Electronic Resource
    Acetaminophen pharmacokinetics in women receiving conjugated estrogen (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 97-98 
    Details
    ISSN: 1432-1041
    Keywords: Acetaminophen ; estrogen ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314814
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  • 14
    Electronic Resource
    Electronic Resource
    Bioinequivalence of marketed diltiazem preparations (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 189-190 
    Details
    ISSN: 1432-1041
    Keywords: Diltiazem ; bioinequivalence ; plasma concentration ; dissolution ; pharmacokinetics ; commercial brands
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A bioequivalence study of three brands of regular diltiazem — Angizem (A), Dilzem (B) and Herbesser (C) has been carried out in 5 healthy, male volunteers. After a single oral dose of 60 mg of each preparation, the mean AUC(0–8 h) and Cmax of preparation B was significantly higher than of brands A and C. The tmax of A and B was significantly lower than of C. B had a higher dissolution rate in vitro (98.8% dissolved in 45 min) than A and C. Thus, there was bioinequivalence of the three brands of diltiazem, due partly to differences in dissolution and perhaps in part to a first pass effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280058
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  • 15
    Electronic Resource
    Electronic Resource
    The effects of frusemide and probenecid on the pharmacokinetics of phenprocoumon (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 261-265 
    Details
    ISSN: 1432-1041
    Keywords: Frusemide ; probenecid ; phenprocoumon ; anticoagulant ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of phenprocoumon with and without co-administration of frusemide and probenecid in two groups of 17 healthy volunteers. Frusemide 40 mg b.i.d. for 7 days did not interact with phenprocoumon to a significant extent. Probenecid 500 mg q.i.d. for 7 days significantly accelerated the overall elimination of phenprocoumon, as indicated by a decrease in AUC from 295 to 157 μg · h · ml−1, and a reduction in the fraction of the dose excreted by the kidneys. The data are consistent with inhibition of the glucronidation of phenprocoumon by probenecid. Its accelerated elimination may be a consequence of the increased formation of hydroxylated metabolites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315107
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  • 16
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of oral noscapine (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 275-279 
    Details
    ISSN: 1432-1041
    Keywords: Noscapine ; pharmacokinetics ; bioavailability ; dose dependency ; oral administration ; inter- and intra-individual variability ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relative bioavailability in 20 healthy volunteers of 100 mg, 200 mg and 300 mg tablets of noscapine and 200 mg as a solution has been assessed in a four-way cross-over study, with repeated administration of the 200 mg dose to assess intraindividual variability. There was a disproportionate increase in the AUC of noscapine tablets, as a 3-fold increase in dose produced a 9-fold rise in AUC. This dose-dependency could mainly be attributed to saturable first-pass metabolism of the drug. Administration of noscapine as a solution resulted in a significantly higher maximal concentration at an earlier time-point and a higher AUC than the corresponding dose as tablets. Repeated administration of noscapine tablets and solution yielded higher AUC on the second dosing occasion. No cause for this carry-over effect was found, and the contribution of remaining noscapine was negligible. The terminal half-life of noscapine, which was independent of formulation or dose size was 4.5 h. Both inter- and intraindividual variability in noscapine kinetics were very high, e.g. 73% and 51% CV of the AUC for the 200 mg tablet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315110
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  • 17
    Electronic Resource
    Electronic Resource
    A multiple dose pharmacokinetic and tolerance study of once daily 200 mg sustained-release flurbiprofen capsules in young and very elderly patients (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 267-270 
    Details
    ISSN: 1432-1041
    Keywords: Flurbiprofen ; sustained-release formulation ; tolerance ; pharmacokinetics ; adverse reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic profile of 200 mg sustained-release flurbiprofen capsules was compared in nine elderly (mean age 84.2 years) and 10 young (mean age 38.1 years) patients with arthritis. After a single capsule, a 48 h plasma concentration profile was performed. The patients then took 1 capsule daily for a further 13 days with plasma levels of the drug being measured pre-dose on alternate days. Following ingestion of the last capsule, a further 48 hour plasma concentration profile was performed. These results were compared with each other and with computer predicted data obtained from dosing with 200 mg conventional flurbiprofen (as 100 mg b.d.). In both young and elderly patients, the two 48 h plasma concentration profiles confirmed the sustained-release characteristics of the capsule. There was no evidence of dose-dumping, although, in one elderly patient with a partial gastrectomy, higher plasma concentrations were observed. Inter- and intra-patient variability was acceptable. A steady-state was achieved within the predicted four days in both groups and there was no evidence of accumulation with the daily dosing interval. A mean steady-state level of approximately 6 μg/ml was achieved for both populations. Computer predicted data for 200 mg conventional flurbiprofen (as 100 mg b.d.) showed a pre-dose/peak range of 1–12 μg/ml. The pre-dose/peak ranges for the young and old patients were 4–10 μg/ml and 4–8 μg/ml respectively. One young patient developed a hypersensitivity reaction of moderate severity; one young and four elderly patients developed a low haemoglobin concentration during the study. No other changes in haematological or biochemical parameters were seen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315108
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  • 18
    Electronic Resource
    Electronic Resource
    Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 165-169 
    Details
    ISSN: 1432-1041
    Keywords: nicotine ; cimetidine ; ranitidine ; pharmacokinetics ; H2-receptor antagonists ; hepatic oxidation ; renal secretion ; tobacco smoking ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomized, double-blind, cross-over experiment, 6 healthy consenting male subjects were administered cimetidine 600 mg or ranitidine 300 mg or placebo p.o. q12h×2 days. Nicotine bitartrate was administered i.v. on day 2 (1 ug/kg/min)×30 min. After cimetidine mean nicotine total and metabolic clearances were decreased by 30% and 27% while after ranitidine the clearances were decreased by 10% and 7% respectively. Since smokers regulate their smoke intake based in large part on their nicotine blood levels these results suggest that the diminished nicotine total clearance in the presence of cimetidine could be important in assisting smoking reduction or cessation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265978
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  • 19
    Electronic Resource
    Electronic Resource
    Sex-difference and the effects of smoking and oral contraceptive steroids on the kinetics of diflunisal (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 175-179 
    Details
    ISSN: 1432-1041
    Keywords: diflunisal ; smoking ; pharmacokinetics ; sex-differences ; oral contraceptive steroids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The single dose pharmacokinetics of diflunisal were studied in 4 groups of 6 young volunteers: control men, control women, women taking low estrogen oral contraceptive steroids (OCS), and women smokers (10–20 cigarettes/day). The plasma clearance of diflunisal was significantly higher in men (0.169 ml·min−1·kg−1) and in women on OCS (0.165 ml·min−1·kg−1) as compared to control women (0.108 ml·min−1·kg−1). Partial metabolic clearances of diflunisal by the three conjugative pathways (phenolic and acyl glucuronide formation, sulphate conjugation) were all increased in men and women OCS users as compared to control women. Statistically significant increases, however, were only observed for the partial metabolic clearance of diflunisal by phenolic glucuronidation between men and women (2.91 vs. 1.85 ml·min−1 respectively), and for the partial clearance by acyl glucuronidation between OCS users and control women (4.81 vs. 3.01 ml·min−1 respectively). Smoking resulted in a moderate increase (35%) in plasma diflunisal clearance. However, a significant reduction in total urinary recovery of diflunisal and its glucuronide and sulphate conjugates was found in smokers (70.5% in smokers as compared to 84.2–87.2% in the 3 other study groups). Consequently, smoking may have induced hydroxylation, a minor oxidative metabolic pathway of diflunisal recently discovered in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265980
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  • 20
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of torasemide and its metabolites in healthy controls and in chronic renal failure (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 345-348 
    Details
    ISSN: 1432-1041
    Keywords: torasemide ; pharmacokinetics ; metabolites ; chronic renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of 20 mg torasemide i.v. has been studied in 7 healthy controls and 9 patients with varying degrees of renal impairment. Torasemide had a t1/2 of about 4 h which was independent of kidney function, as the nonrenal clearance of torasemide was 3-times greater than its renal clearance. The active metabolite M1 and the main metabolite M5 were accumulated in chronic renal failure. In contrast to liver function, therefore, kidney failure does not have an important effect on the pharmacokinetics of torasemide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315407
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  • 21
    Electronic Resource
    Electronic Resource
    The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 327-332 
    Details
    ISSN: 1432-1041
    Keywords: Hypertension ; perindopril ; hydrochlorothiazide ; ACE inhibition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic effects and acceptability of perindopril (4 mg daily) and hydrochlorothiazide (25 mg daily) given alone or in combination for 1 month were investigated in a double-blind, placebo controlled, parallel group study. The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups. Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide (11/7 mm Hg supine) given alone at these doses. The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure (24.5/12.6 mm Hg supine) taking into account the placebo response. The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide. The formation of perindoprilat was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group. Perindopril, whether given alone or in combination with hydrochlorothiazide, was well tolerated and produced no clinically significant change in routine haematology or serum biochemistry. The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315404
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  • 22
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of the ace inhibitor benazepril hydrochloride in the elderly (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 379-385 
    Details
    ISSN: 1432-1041
    Keywords: benazepril ; benazeprilat ; ACE inhibitor ; pharmacokinetics ; pharmacodynamics ; elderly ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of a single oral dose benazepril·HCl 10 mg have been studied in 15 healthy volunteers aged 65 to 80 y. The kinetics of unchanged benazepril and its active metabolite benazeprilat did not differ significantly in males and females, so the combined kinetic data from all 15 elderly subjects were compared with a historical control group of 19–32 year-old healthy men treated in the same way. The disposition of benazepril was not affected by age. The time to maximum plasma concentration, tmax (0.5 h) and elimination half-life (0.6 h) in the elderly were the same as in young subjects. The kinetics of benazeprilat was slightly changed in the elderly; although its tmax (1.5 h) was not affected, Cmax and the AUC were 20–40% greater. The elimination half-life of benazeprilat during the first 24 h after doing in the elderly was increased by about 20% to 3.2 h. The renal plasma clearance of benazeprilat (18.1 ml·min−1) was about 20% smaller than in the young subjects. An average of 18.5% of the dose was recovered as benazeprilat in the 24 h urine from the elderly subjects, which was similar to the recovery in the young subjects. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 95%, respectively). Mean systolic and diastolic blood pressures in the elderly were reduced by a maximum of 37/16 mm Hg at 6 h, in association with a small rise in pulse rate. Treatment was generally well tolerated. Three of the 15 subjects reported clinical adverse experiences judged to be possibly drug related, namely headache, abdominal pain and cold extremities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315579
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  • 23
    Electronic Resource
    Electronic Resource
    Oral pharmacokinetics of pirenzepine in patients with chronic renal insufficiency, failure, and maintenance haemodialysis (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 405-406 
    Details
    ISSN: 1432-1041
    Keywords: pirenzepine ; renal insufficiency ; haemodialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic properties of pirenzepine following administration of a single, 50 mg oral dose were evaluated in three groups of subjects: group I, end stage renal disease requiring maintenance haemodialysis (CLCR 0 to 10 ml·min−1); group II, moderate renal insufficiency (CLCR 10 to 30 ml·min−1); and group III, mild renal dysfunction (CLCR 30 to 70 ml·min−1). Additionally, subjects in group I received a 50 mg dose on a non-dialysis day and at least one week later, a 50 mg dose during haemodialysis. There was a linear relationship (r = 0.97) between pirenzepine renal clearance and renal function as measured by creatinine clearance. The harmonic mean terminal half-life for pirenzepine was 17.3 h in subjects with end stage renal disease, 18.0 h in subjects with moderate renal insufficiency and 14.7 h in subjects with mild renal dysfunction. Haemodialysis reduced the level of circulating pirenzepine by approximately 25%. The mean arterial to venous plasma pirenzepine ratio during hemodialysis was 1.29 (range 1.02–1.56). Based on subjective reporting of adverse experiences and clinical observation, pirenzepine appeared to have had a wide margin of safety in these patients. Dry mouth was the most frequently reported adverse experience attributable to pirenzepine administration. A reduction in dose or dosing frequency may be warranted only in end state renal disease (CLCR 0 to 10 ml·min−1).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315586
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  • 24
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of S(+)- and R(−)-ibuprofen in volunteers and first clinical experience of S(+)-ibuprofen in rheumatoid arthritis (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 493-497 
    Details
    ISSN: 1432-1041
    Keywords: ibuprofen ; rheumatoid arthritis ; enantiomer ; stereoselectivity ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary S(+)-, R(−)- or racemic ibuprofen was administered orally to volunteers in doses of 150 mg, 300 mg and 500 mg pure S(+)-, 300 mg pure R(−)- and 600 mg racemic ibuprofen. The pharmacokinetic parameters in humans showed that S(+)-ibuprofen was not inverted to R(−)-ibuprofen, whereas R(−)-ibuprofen was inverted to S(+)-ibuprofen to a variable degree. S(+)-ibuprofen and R(−)-ibuprofen given alone more rapidly reached significantly higher maximal plasma concentrations than after the same doses of the racemic compound. The elimination half-lives and clearance values for all three forms of ibuprofen were comparable. The mean residence time of S(+)-ibuprofen after R(−)- and racemic ibuprofen was significantly longer than after administration of the pure S(+)-enantiomer. Judged by the AUC, the bioavailability of S(+)-ibuprofen was independent of the dose within the range tested. Administration of S(+)-ibuprofen to 6 rheumatic patients showed that the pharmacokinetic behaviour of S(+)-ibuprofen in patients was similar to that found in volunteers. S(+)-ibuprofen proved to be an effective analgesic antirheumatic drug in the dose range 1 to 1.5 g/day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02336690
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  • 25
    Electronic Resource
    Electronic Resource
    Pharmacokinetics, cerebrospinal fluid concentration, and safety of intravenous rifampin in pediatric patients undergoing shunt placements (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 515-517 
    Details
    ISSN: 1432-1041
    Keywords: rifampicin ; cerebrospinal fluid ; children shunt infections ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations and safety of intravenous rifampin in pediatric patients undergoing shunt placement. Nine patients (mean age 5.6 y) received a single dose of rifampin, 20 mg · kg−1, administered intravenously 1 h prior to surgery. The peak serum concentrations ranged from 13.5–26.7 μg · ml−1; cerebrospinal fluid concentrations ranged from 0.12–3.0 (mean: 1.4) μg · ml−1. The mean total clearance, apparent distribution volume, and elimination half-life were 0.291 · kg−1 · h−1, 1.11 · kg−1, and 2.8 h. The concentrations of rifampin achieved in the cerebrospinal fluid exceeded the minimum inhibitory concentrations by 100-to 1000-fold against Staphylococcus epidermidis. However, 5 of 9 patients developed cutaneous reactions during intravenous rifampin prophylactic therapy. Because of the high frequency of adverse effects and more than adequate rifampin concentrations achieved in the cerebrospinal fluid, rifampin doses lower than that used in this study may be evaluated in future studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02336694
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  • 26
    Electronic Resource
    Electronic Resource
    Excretion of tolbutamide metabolites in young and old subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 523-524 
    Details
    ISSN: 1432-1041
    Keywords: tolbutamide ; hydroxytolbutamide ; carboxytolbutamide ; urinary excretion ; age ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolbutamide (1 g/70 kg) was administered as a single intravenous dose to 31 healthy, non-smoking, drug-free males between 23 and 87 years old and the total amounts of hydroxy and carboxytolbutamide excreted in 24 h were measured. There was a significant decrease in the urinary recovery of both metabolites with age. The reason for these findings is not known at the present time and may be associated with the decrease in creatinine clearance observed in these subjects or other changes in the pharmacokinetics of tolbutamide which are currently being investigated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02336696
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  • 27
    Electronic Resource
    Electronic Resource
    Effect of posture on total phenytoin plasma concentration (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 526-527 
    Details
    ISSN: 1432-1041
    Keywords: phenytoin ; posture ; pharmacokinetics ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02336698
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  • 28
    Electronic Resource
    Electronic Resource
    Comparative enantioselective pharmacokinetic studies of celiprolol in healthy volunteers and patients with impaired renal function (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 573-576 
    Details
    ISSN: 1432-1041
    Keywords: celiprolol ; renal failure ; pharmacokinetics ; enantioselective kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the ß1-selective adrenergic antagonist (R,S)-celiprolol has been studied after oral administration of 200 mg celiprolol-HCl to 8 healthy volunteers and 8 patients with various degrees of impaired renal function. No significant difference was found between the two enantiomers in the control group or in the patients. In healthy volunteers an average of 9.8% of the dose of R-(+)-celiprolol and 9.5% of S-(-)-celiprolol was recovered unchanged in the urine. Renal impairment reduced the urinary excretion of both enantiomers to the same extent according to the severity of the uraemia, producing higher AUCs. Nevertheless, the terminal half-lives of the R- and S-enantiomers were not significantly different between the groups. Dosage reduction in patients with renal impairment does not seem to be necessary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316098
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  • 29
    Electronic Resource
    Electronic Resource
    Rapid and slow benzbromarone elimination phenotypes in man: benzbromarone and metabolite profiles (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 577-581 
    Details
    ISSN: 1432-1041
    Keywords: Benzbromarone ; elimination phenotypes ; pharmacokinetics ; metabolism ; genetic variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following oral administration of the uricosuric drug benzbromarone two major metabolites appear in the circulation, 1'-hydroxy-benzbromarone (M1), and a second product (M2) of unknown structure. The plasma concentrations of the parent drug and of M1 and M2 have now been compared in two different elimination phenotypes, 10 subjects who eliminated the drug rapidly (S1–10) and one individual (S11) whose elimination capacity was impaired, presumably due to genetic variation (S11). The AUC (0–96) of the parent drug in S11 was 145 gmg · ml−1 h, and in the other individuals it averaged 18.3 (11.4–24.5) μg · ml−1 h. The plasma elimination half life of benzbromarone was 3.34 (1.77–5.24) h in the rapid eliminators, and 13.08 h in the subject with the elimination defect. The mean plasma elimination half life of the metabolites in S1–10 amounted to 20.1 (11.9–41.2) h for M1, and 17.2 (12.9–30.7) h for M2. In S11 the plasma elimination half life of M1 was prolonged to 76.6 h, and of M2 to 75.4 h. Thus, the elimination defect in S11 was not restricted to the parent drug, but it also involved the two major metabolites M1 and M2. This might be a consequence of a hepatic enzyme deficiency, or be due to impairment of drug excretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316099
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  • 30
    Electronic Resource
    Electronic Resource
    Comparative bioavailability of a cisapride suppository and tablet formulation in healthy volunteers (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 629-631 
    Details
    ISSN: 1432-1041
    Keywords: Cisapride ; pharmacokinetics ; bioavailability ; suppository ; tablet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The comparative bioavailability of cisapride as a 30 mg suppository and three 5 mg oral tablets was investigated in 12 non-smoking, healthy male volunteers. The two formulations were administered on two separate occasions following an overnight fast, according to a randomized cross-over design. The plasma concentration of cisapride was measured over 48 h after drug administration. The 30 mg suppository exhibited a mean time to the peak plasma concentration of 3.8 h, while the tablets showed a significantly earlier peak time of 1.5 h. The maximum plasma concentration of cisapride after the 30 mg suppository (50.3 ng · ml−1) was significantly lower than after the tablets (74.3 ng · ml−1). The AUCs following the two treatments did not differ significantly from each other. The comparative bioavailability of the 30 mg cisapride suppository in relation to the three 5 mg oral tablets was 85%, with a 95%-confidence interval of 67% to 102% (not adjusted for dose). Normalizing the mean AUC by dose, the relative bioavailability of the suppository was 43% of that of the tablet. The elimination half-life of cisapride was not significantly different following the administration of the two formulations (9.3 h for the suppository and 9.8 h for the tablet).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278595
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  • 31
    Electronic Resource
    Electronic Resource
    Relationship between pharmacokinetics and hemodynamic tolerance to isosorbide-5-mononitrate (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. S53 
    Details
    ISSN: 1432-1041
    Keywords: nitrates ; pharmacokinetics ; pharmacodynamics ; nitrate tolerance ; isosorbide-5-mononitrate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Healthy male volunteers received three different dose regimens of a controlled-release form of isosorbide-5-mononitrate (IS-5-MN; 60 mg per tablet). Dose regimen I consisted of a single daily dose of 60 mg given for 5 days. Dose regimen 11 was started with a dose of 60 mg, followed by 30 mg 12 h later and thereafter every 8 h. The last dose, on the 5th day was again 60 mg. In dose regimen III60 mg followed by 30 mg 6 h later were administered every day for 5 days. The peripheral arterial and venous effects of IS-5-MN during the first and last dosing interval were followed by changes in the finger pulse curve, standing systolic blood pressure, heart rate, and venous distensibility. Plasma concentrations of IS-5-MN were measured frequently following the first and the last dose. Following dose regimen I all hemodynamic effects produced by the first dose were maintained during the study. The maximal plasma concentrations were about 400 ng/ml and the trough value, lower than 100 ng/ml. Following dose regimen II the hemodynamic effects of IS-5-MN and sublingual glyceroltrinitrate were completely abolished on the 5th day. Trough plasma concentrations were approximately 300 ng/ml during the entire study period. Following dose regimen III pronounced hemodynamic effects were seen on the 1st day. However, a significant attenuation of the hemodynamic effects was measured on the 5th day, when trough plasma concentrations were between 100 and 230 ng/ml. There was a significant negative correlation between the magnitude of hemodynamic effect remaining on the 5th day (measured by the area under the finger pulse curve) and the trough plasma concentration. Thus, the maintenance of minimum plasma concentrations of IS-5MN of 300 ng/ml or higher produces a rapid development of hemodynamic nitrate tolerance, whereas no tolerance was found when the plasma concentrations were allowed to decline below 100 ng/ml before the next dose was given. A significant attenuation of hemodynamic effects was found when minimum plasma concentrations were between 100 and 230 ng/ml. The degree of attenuation in this concentration range increased with increasing trough plasma concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01417565
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  • 32
    Electronic Resource
    Electronic Resource
    Uricosuric effect of different doses of irtemazole in normouricaemic subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 489-491 
    Details
    ISSN: 1432-1041
    Keywords: irtemazole ; dose-response relationship ; pharmacokinetics ; uricosuric drugs ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Irtemazole 12.5 to 50 mg in 6 healthy, normouricaemic subjects caused a maximal decrease in plasma uric acid (after 8 to 12 h) of 46.5%. The uricosuric effect began during the first 60 min after drug administration and it lasted for 7 to 24 h. Renal uric acid excretion returned to its base line value after 8 to 16 h and uric acid clearance after 10.0 to 12.0 h. Doses of irtemazole between 12.5 and 37.5 mg produced a dose-related rise in the uricosuric effect. There was no essential difference between the uricosuric effect of 37.5 mg and 50 mg irtemazole. The D50 dose (that producing a half-maximal effect) was between 16.3 mg and 34.2 mg, (average 24.7 mg). The value of irtemazole in the management of hyperuricaemia and gout remains to be determined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02336689
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  • 33
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of cicaprost in healthy volunteers after oral administration of 5 to 20 μG (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 149-153 
    Details
    ISSN: 1432-1041
    Keywords: Cicaprost ; PGI2-mimetic drug ; pharmacokinetics ; pharmacodynamics ; volunteers ; dose titration ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a Phase I study, the tolerability, pharmacodynamics and pharmacokinetics of cicaprost have been investigated in 6 male volunteers given 5, 10, 15 and 20 μg as tablets of the β-cyclodextrin clathrate. Individual inhibition of platelet aggregation and changes in facial colour (measured by chromametry) were dose-dependent and reached a maximum 30 to 60 min post-dose. The maximum inhibition of platelet aggregation was about 40%. After 3 to 4 h pre-treatment values had returned. Blood pressure remained within the normal range. The peak plasma level of cicaprost was reached within 15 to 90 min after drug intake. Both Cmax-and AUC were individually dose-dependent. The terminal half-life in plasma of cicaprost was approx. 1 h, and its total clearance amounted to 4–7 ml·min−1·kg−1. The time courses of the plasma levels and of the pharmacodynamic actions were in agreement. Interindividual differences were observed in the occurrence of unwanted effects (e.g. headache). Thus, cicaprost is an orally available PGI2-mimetic, for which effects on platelet aggregation and vascular perfusion have been demonstrated in healthy volunteers after doses of 5 to 15 μg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280049
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  • 34
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and protein binding of methocarbamol in renal insufficiency and normals (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 193-194 
    Details
    ISSN: 1432-1041
    Keywords: methocarbamol ; haemodialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We determined plasma methocarbamol concentrations over 24 h following a 1.5 g methocarbamol dose (off-dialysis day) to 8 chronic haemodialysis patients and compared these results to those from 17 healthy male volunteers. The harmonic mean elimination half-life was similar between the two groups, 1.24 and 1.14 h, respectively. tmax and the weight-adjusted Cmax were 1.1 h and 27.0 mg · m−1 for haemodialysis patients and 1.1 and 23.1 mg · l−1 for normals. Relative systemic availability was assessed by comparing weight-normalized AUC × k10 products. These results indicate no significant differences with respect to methocarbamol absorption, with the relative systemic availability in patients being 113%. These data suggest that absorption and elimination of methocarbamol is similar between normal subjects and patients undergoing maintenance haemodialysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280060
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  • 35
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of various single intravenous and oral doses of omeprazole (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 195-197 
    Details
    ISSN: 1432-1041
    Keywords: Omeprazole ; metabolites ; bioavailability ; pharmacokinetics ; dose-dependent kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of dose on the kinetics of omeprazole and two of its metabolites, hydroxyomeprazole and the sulphone, has been studied. Ten healthy subjects were given omeprazole 10 and 40 mg iv and 10, 40 and 90 mg orally. No significant dose-related difference in any parameter calculated from the iv experiments was detected. Following the oral solutions, however, there was a dose-dependent increase in systemic availability, probably due to saturable first-pass elimination. The AUC of the sulphone also seemed to increase non-linearly with increasing dose, and that of the hydroxyomeprazole increased in proportion to dose. The slight dose-dependency of the bioavailability of the solution is considered to be of no or limited clinical relevance. Furthermore, since omeprazole is given orally as slowly absorbed enteric coated granules in the dose of 20 mg o.d., the potential for dose-dependent kinetics in clinical practice would be much less than in the present study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280061
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  • 36
    Electronic Resource
    Electronic Resource
    Chronokinetic study of netilmicin in man (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 199-201 
    Details
    ISSN: 1432-1041
    Keywords: netilmicin ; pharmacokinetics ; diurnal variation ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Netilmicin 1.5 mg/kg body weight was administered intravenously every 8 h for 2 days to 8 patients with normal renal function. Significant elevation of mean and trough plasma concentrations was found at 05.00 h and 09.00 h. This was considered to be due to circadian variation, with possible accumulation during the night. The clinical importance of this phenomenon in relation to the development of aminoglycoside toxicity awaits further investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280062
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  • 37
    Electronic Resource
    Electronic Resource
    Impairment of estramustine phosphate absorption by concurrent intake of milk and food (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 189-193 
    Details
    ISSN: 1432-1041
    Keywords: estramustine phosphate ; prostatic cancer ; gastrointestinal absorption ; food intake ; calcium ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of milk and food on the pharmacokinetics of estramustine phosphate was investigated in six patients with prostatic cancer. In a randomized three-way cross-over study, the patients were given single doses of the drug together with low calcium water, low calcium food and milk. The evaluation was based upon the plasma concentration of two metabolites, estromustine and estrone, as parent drug could not be detected in plasma. The tmax and lag time of estromustine were significantly increased by milk and food intake and Cmax and AUC were significantly decreased. In comparison with water, the AUC of estromustine was 41% when the drug was taken with milk and 67% after simultaneous intake of standardized food. Corresponding figures for the peak values were 32 and 57%, respectively. The effect of milk and food intake on the pharmacokinetics of estrone was similar. Studies in vitro demonstrated that the dissolution of estramustine phosphate disodium was markedly impaired in the presence of calcium. It was concluded that the rate and extent of absorption of estramustine phosphate were decreased when the drug was taken with milk or food due to the formation of a poorly absorbable calcium complex. To obtain high and reproducible absorption of Estracyt®, the drug should not be taken together with milk, milk products or other calcium-rich food or drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265983
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  • 38
    Electronic Resource
    Electronic Resource
    The pharmokinetics of isradipine in hypertensive subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 209-211 
    Details
    ISSN: 1432-1041
    Keywords: Isradipine ; hypertension ; pharmacokinetics ; pharmacodynamics ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In conjunction with a multicentre clinical trial of the calcium antagonist isradipine in hypertension, pharmacokinetic and pharmacodynamic studies were conducted in 9 subjects. An initial dose of 5 mg (capsule formulation) of isradipine was given orally. The mean Cmax, tmax and AUC(0–8) were 6.0 ng · ml−1, 1.5 h and 15.1 h · ng · ml−1 respectively. Seven subjects repeated the study at steady state after 10 week's dose titration with isradipine. Cmax, tmax and AUC(0–8) were 3.7 ng · ml−1, 1.2 h and 12.2 h · ng · ml−1 respectively indicating that the drug does not accumulate over time. Control of blood pressure paralleled plasma isradipine concentrations which suggested that the drug should be given at least twice daily. Pharmacokinetic studies performed in conjunction with clinical trials can provide valuable information about the patterns of drug response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265988
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  • 39
    Electronic Resource
    Electronic Resource
    Excessive motor impairment two hours after Triazolam in the elderly (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 229-232 
    Details
    ISSN: 1432-1041
    Keywords: benzodiazepines ; elderly subjects ; excessive drug effect ; psychomotor performance ; pharmacokinetics ; adverse reaction ; age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of triazolam 0.25 mg p.o. and psychomotor coordination were compared in nine healthy, elderly volunteers and nine middle aged controls. Motor coordination, as measured by pursuit rotor performance, was impaired in the elderly even before triazolam administration, and in contrast to the controls it deteriorated to a critical level after the drug. Factors associated with the major decrease in psychomotor performance in the elderly volunteers were poor baseline performance, an additional independent-age factor, and the plasma concentration of free triazolam. Although short acting benzodiazepines may have a less detrimental effect on performance on the morning following their intake, there may be serious motor incoordination and falls may occur if the patients have to rise during the night, particularly when the plasma concentration is high, i.e. about 2 h after dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315021
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  • 40
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of conventional and controlled-release formulations of metipranolol in man (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 243-247 
    Details
    ISSN: 1432-1041
    Keywords: metipranolol ; pharmacokinetics ; pharmacodynamics ; β-adrenoreceptor blockade ; radioreceptor assay ; controlled release form
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and β-adrenoceptor blocking effects of conventional and sustained-release metipranolol have been studied in 6 healthy male volunteers given a single oral dose of 40 mg. Plasma drug concentrations determined by TLC and a radioreceptor assay, and the inhibition of exercise-induced tachycardia, were monitored for 48 h. Relevant amounts of active metabolites other than deacetylmetipranolol were not found. Compared to conventionally formulated metipranolol, the controlled-release product had a prolonged mean residence time (10.7 vs 5.5 h), the peak drug concentration was halved and the time to peak drug concentrations was delayed. Relatively constant plasma concentrations (cideal = 6.5 ng/ml) and a clinically significant reduction of exercise-induced tachycardia were maintained throughout a 24 h dosing interval. An individual deacetylmetipranolol plasma concentration-effect relationship was evaluated using the Emax model. Mean parameters were Emax 26% and C50 2.9 ng/ml.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315024
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  • 41
    Electronic Resource
    Electronic Resource
    Effect of mequitazine on the pharmacokinetics of theophylline in asthmatic patients (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 255-258 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; mequitazine ; drug interaction ; pharmacokinetics ; asthma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of an oral anti-allergic drug, mequitazine, on the pharmacokinetics of theophylline has been investigated in seven asthmatic patients. They received chronic theophylline therapy (a sustained-release theophylline tablet 200–400 mg b.d. at 12 h intervals) and coadministered mequitazine 6 mg for 3 weeks. Plasma theophylline concentration-time curves and the urinary excretion of theophylline and its major metabolites before and after coadministration of mequitazine were compared. No significant change in the pharmacokinetic parameters of theophylline or in the urinary recovery of unchanged drug and its metabolites was observed. Thus, mequitazine did not influence the pharmacokinetics of theophylline and it should be safe for coadministration to asthmatic patients on chronic theophylline therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315026
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  • 42
    Electronic Resource
    Electronic Resource
    Altered flecainide disposition in healthy volunteers taking quinine (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 269-273 
    Details
    ISSN: 1432-1041
    Keywords: flecainide ; quinine ; pharmacokinetics ; metabolism inhibition ; drug interaction ; renal transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of flecainide and its two sequential metabolites, both free and conjugated, its pharmacodynamics, and the influence of simultaneously administered quinine, have been studied in 10 healthy subjects. The study comprised two, 48-h open phases at an interval of 1 week. Flecainide acetate 150 mg was given as a 30-min i.v. infusion and quinine sulphate orally 500 mg×3 over 24 h. Quinine administration did not change the apparent volume of distribution or the renal clearance of flecainide, but it significantly reduced its systemic clearance (9.2 vs 7.6 ml · kg−1 · min−1), thus increasing the elimination half-life (9.6 vs 11.5 h). The amount of flecainide transformed to its first, meta-O-dealkylated metabolite (MODF) fell with no change in the renal excretion of the latter, either in its free or conjugated forms. This finding, in association with a fall in amount of the second, meta-O-dealkylated lactam metabolite (MODLF) recovered in its conjugated forms in the urine, suggests that quinine inhibits both the first and the second steps of the sequential metabolism of flecainide. When the subjects received quinine in addition to flecainide, the PR interval in the ECG was slightly more prolonged than with flecainide alone. Due to the study design, an effect of quinine per se and the consequence of increased serum flecainide levels could not be distinguished.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315029
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  • 43
    Electronic Resource
    Electronic Resource
    Stereoselective pharmacokinetics of tocainide in human uraemic patients and in healthy subjects (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 373-376 
    Details
    ISSN: 1432-1041
    Keywords: tocainide ; uraemia ; enantiomers ; stereoselective ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of tocainide enantiomers were examined in healthy human subjects and uraemic patients following a single i. v. dose (200 mg) of racemic tocainide hydrochloride. In the healthy subjects, the total body clearance of R(−)-tocainide was significantly greater than that of S(+)-tocainide (2.62 vs 1.70 ml·min−1·kg−1). Renal clearance also favoured R(−)-tocainide and appeared to contribute significantly to the stereoselective total body clearance. The volume of distribution of the enantiomers did not differ significantly. Uraemia produced a marked decrease in the total body clearance with no apparent effect on the volume of distribution of both enantiomers. The S/R ratio for total body clearance decreased significantly from 0.66 in healthy subjects to 0.54 in the uraemics, while the ratio for terminal elimination half-life significantly increased from 1.43 to 1.59. These results indicate that uraemia alters the degree of stereoselectivity in the pharmacokinetic parameters of tocainide enantiomers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315413
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  • 44
    Electronic Resource
    Electronic Resource
    Pharmacokinetic study of methotrexate, folinic acid and their serum metabolites in children treated with high-dose methotrexate and leucovorin rescue (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 377-383 
    Details
    ISSN: 1432-1041
    Keywords: Methotrexate ; folinic acid ; 7-hydroxymethotrexate ; pharmacokinetics ; 5-methyltetrahydrofolic acid ; leucovorin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of methotrexate (MTX), 7-hydroxymethotrexate (7-OHMTX), 2,4-diaminomethylpteroic acid (APA), folinic acid, and 5-methyltetrahydrofolate (5-MTHF) have been studied during 21 high-dose MTX (HDMTX) infusions (5 g·m−2 in 24 h) with leucovorin (LCV) rescue, a component of the therapy of 5 children with acute lymphoblastic leukemia (ALL). The median steady-state concentration of MTX was 66 μmol·l−1. Three elimination half-lifes were determined for MTX: 1.8 h, 6.4 h and a terminal 15 h. The median systemic MTX clearance was 110 mg·m−2·min−1. The 7-OHMTX level increased during each infusion and a Cmax of 19 μmol·l−1 was achieved at the end. Its initial half-life was 5 h and the terminal half-life was 12 h. Thus, the peak serum concentration ratio of 7-OHMTX to MTX was reached 24 h after the end of the infusion at a median ratio of 8. The MTX metabolite APA was detected in concentrations less than 0.06 μmol·l−1. The median folinic acid level during rescue, 48 h after starting the infusion, was 7.0 μmol·l−1 and 18 h following the last dose of LCV it was 0.44 μmol·l−1, leading to ratios of folinic acid to MTX of 31 and 6, respectively. The median 5-MTHF level during rescue was 0.44 μmol·l−1 with a median ratio of 5-MTHF to MTX of 2. Twenty infusions with 48 h MTX levels of less than 0.5 μmol·l−1 were without marked toxicity. Only one patient with a 48 h MTX concentration of 5.5 μmol·l−1 and a ratio of 5-MTHF to MTX of 0.08 suffered from ulcerating mucositis and septicaemia despite increased and prolonged LCV rescue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315414
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  • 45
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and effects of levodopa in advanced Parkinson's disease (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 385-389 
    Details
    ISSN: 1432-1041
    Keywords: Levodopa ; Parkinson's disease ; pharmacokinetics ; pharmacodynamics ; modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with severe Parkinson's disease were characterized with respect to their pharmacokinetic and pharmacodynamic responses to levodopa given: orally, intravenously (three different infusion rates) and intraduodenally. The best therapeutic infusion rate in the intravenous study was used for the intraduodenal infusion of levodopa. A lag time between plasma concentration and effect following oral administration was seen in three of the five patients and this disequilibrium was estimated as the rate constant ke0 using model-independent analysis. The plasma concentration-effect relationship was similar for the three modes of administration and in all patients the therapeutic plasma concentration for full mobility was 〉4–5 μg·ml−1. The disequilibrium half-life for development of effect after oral administration was calculated to be about 30 min. The patients remained clinically stable during the period of the intraduodenal infusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315415
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  • 46
    Electronic Resource
    Electronic Resource
    Effect of exercise on propranolol pharmacokinetics (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 391-394 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; beta-blockers ; pharmacokinetics ; exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of submaximal exercise on the pharmacokinetics of low dose intravenous propranolol was studied in 15 healthy human subjects. There was a wide individual variation in the results for each subject and a large difference in the degree of changes with exercise. The effect of exercise on the pharmacokinetics of propranolol, a flow limited drug, is marked but variable. This phenomenon may have profound effects on patients taking the drug regularly who exercise intermittently and drug doses may have to be adjusted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315416
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  • 47
    Electronic Resource
    Electronic Resource
    The effect of exercise on atropine pharmacokinetics (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 395-397 
    Details
    ISSN: 1432-1041
    Keywords: atropine ; exercise ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy males (19–32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 2321). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 1981), and clearance (CL, 763 vs 638 ml·min−1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng·ml−1) and area under the curve (AUC, 44.1 vs 53.1 ng·ml−1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml·min−1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min−1), elimination rate constant (ke, 0.0012 vs 0.0015 min−1), Cp (14 ng·ml−1) and AUC (53.3 ng·h·ml−1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315417
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  • 48
    Electronic Resource
    Electronic Resource
    Yohimbine bioavailability in humans (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 409-411 
    Details
    ISSN: 1432-1041
    Keywords: yohimbine ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic profiles were determined in seven healthy young male subjects following single oral and intravenous doses of 10 mg of yohimbine hydrochloride. The drug was rapidly eliminated (t1/2β 0.58 h orally and t1/2β 0.68 h intravenously). Following intravenous administration the data fit a two-compartment pharmacokinetic model, with a very rapid distribution phase (t1/2a was approximately 6 min). Both the oral and the intravenous yohimbine clearance values were high but oral clearance values were much higher (mean 9.77 ml·min−1·kg−1 intravenous versus 55.9 ml·min−1·kg−1 oral). The oral bioavailability showed great variability, ranging from 7% to 87% (mean value was 33%). The imcomplete oral bioavailability of yohimbine may reflect either incomplete absorption from the gastrointestinal tract or an hepatic first pass effect. Although yohimbine is rapidly absorbed when given orally, the bioavailability is quite variable and considerable individualization of dosing may be necessary when the drug is used orally for clinical indications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315421
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  • 49
    Electronic Resource
    Electronic Resource
    Two-stage penetration of a single oral dose of sulphadimethoxine into skin blister fluid (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 487-490 
    Details
    ISSN: 1432-1041
    Keywords: sulphadimethoxine ; plasma concentration ; skin blister fluid concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-dependent concentration curves of sulphadimethoxine in plasma and cantharidin-induced skin blister fluid have been evatuated following a single oral dose of 1 g. In contrast to other drugs, sulphadimethoxine exhibited two-stage penetration into the blister fluid, the second peak concentration being higher than the first. The maximum plasma concentration of 94.1 mg·l−1 was observed after 4 h, and in skin blister fluid the first peak of 25.6 mg·l−1 was found after 7 h, and the second of 58.0 mg·l−1 occurred after 30 h. The penetration of sulphadimethoxine into skin blister fluid, defined as the ratio of the AUC there to that in plasma was 0.748. The results suggest that sulphadimethoxine penetrates into skin blister fluid to a great extent from plasma and achieves concentrations exceeding the MIC for susceptible pathogens, but it requires a relatively long time to do so.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280941
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  • 50
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of d-sotalol and d,l-sotalol in healthy volunteers (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 579-582 
    Details
    ISSN: 1432-1041
    Keywords: d-sotalol ; d,l-sotalol ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of d-sotalol has been studied in six healthy volunteers given single doses of 0.25, 0.50, 1, 2 mg·kg−1 i.v. and one 100 mg oral dose in comparison with the kinetics of 1 mg·kg−1 i.v. of dlsotalol. There was no significant difference in the disposition of the d-enantiomer and the racemate. The terminal half-life averaged 7.2 h, and the kinetics was linear, with a mean total clearance of 0.13 l·h−1·kg−1. Renal clearance of d-sotalol represented 56 to 77% of total clearance. The absolute systemic availability of oral d-sotalol was close to 100% and the elimination half-life of the oral-d-enantiomer was similar to that of the i.v. form (7.5 h).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278585
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  • 51
    Electronic Resource
    Electronic Resource
    Subjective symptoms and pharmacokinetics/dynamics of metoprolol CR in elderly subjects — a comparison with atenolol (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 571-578 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; metoprolol CR ; elderly subjects ; subjective symptoms ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, randomised, cross-over study, the pharmacokinetic/dynamic effects and subjective symptoms of a new controlled-release (CR) formulation of metoprolol (50 and 100 mg) have been compared with atenolol (50 mg) and placebo in 20 elderly healthy subjects. The metoprolol CR formulation displayed an even plasma concentration-time profile over the dosage interval while atenolol produced a peak at 2–4 h. All three active treatments produced significant β1-blockade at 24 h compared to placebo. Four hours after dose intake, the degree of β1-blockade was significantly greater with conventional atenolol 50 mg than with either dose of metoprolol CR. Subjective well-being was examined with a self-administered questionnaire (MSE-profile), including three dimensions: Contentment, Vitality and Sleep. No significant differences were detected between placebo and either dose of metoprolol CR. At 2 h, following atenolol, a deterioration in Vitality was observed compared to placebo and metoprolol CR 100 mg. At the end of the dosage interval there was no longer any significant difference between the treatments. Perceived leg fatigue during exercise, evaluated 4 h after dosing, was more pronounced during treatment with atenolol than metoprolol CR 50 mg. The results suggest that the metoprolol CR formulation was not associated with significant effects on subjective well-being, whereas atenolol caused a deterioration at the time of the peak plasma concentration of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278584
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  • 52
    Electronic Resource
    Electronic Resource
    Single- and multiple-dose pharmacokinetics of R-(−)- and S-(+)-prenylamine in man (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 587-593 
    Details
    ISSN: 1432-1041
    Keywords: prenylamine ; racemic drug ; stereoselectivity ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of S-(+)- and R-(−)-prenylamine was studied in eight healthy volunteers given single and repeated oral doses of the racemic drug. Distinct differences in various pharmacokinetic parameters were found between the S- and R-enantiomer. The maximum plasma concentrations and AUCs of the R-enantiomer exceeded those of the S-enantiomer five-fold; the apparent oral clearance of the S-form was five-times and the renal clearance three-times higher than of the R-form. Acid catalyzed hydrolysis of urine samples released more S-prenylamine, indicating stereoselective glucuronidation of unchanged prenylamine. Plasma protein binding also differed between the two enantiomers, generally with a higher unbound fraction of the S-form, whereas analysis of the bound fractions showed that prenylamine was bound to different plasma proteins with inverse stereoselectivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278587
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  • 53
    Electronic Resource
    Electronic Resource
    Circadian influence on effect of propranolol on exercise-induced tachycardia in healthy subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 133-137 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; chronopharmacology ; exercise-induced tachycardia ; pharmacokinetics ; healthy volunteers ; gastio-intestinal absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following a cross-over design propranolol 20 mg p.o. was given to 7 healthy subjects at 09.00 h and 21.00 h at an interval of 1 week. Heart rate (HR) during submaximal ergometer exercise was measured at four intervals during 10 h after treatment. Plasma propranolol concentrations were also determined. The suppressive effect (%R) of propranolol on the rise in HR during exercise after the morning dosage was significantly greater at 1.5 h and tended to be greater 3 h after administration than at comparable times in the evening trial. Mean plasma propranolol concentrations during the early phase were higher after the morning than the evening dose. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve from 0 to 10 h (AUC (0–10)) and absorption rate constant (ka) were significantly greater after the morning dose. The time to maximum concentration (tmax) and elimination half-life (t1/2) of the morning and evening dosages did not differ. A significant correlation was observed between plasma propranolol concentration and %R in HR during exercise in the morning (r=0.74) and evening (r=0.63) trials, and the regression lines of the morning and evening treatments did not differ. The data indicate that the suppressive effect of propranolol on exercise-induced tachycardia was relatively greater after a morning than an evening dose; that propranolol was more rapidly absorbed from the gastrointestinal tract after the morning than the evening dosage; that diurnal changes in the activity of propranolol depend in part on the time of administration and its subsequent effect on plasma concentrations of the drug; and that the antagonist activity of propranolol relative to a given drug concentration may not differ between morning and evening treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265971
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  • 54
    Electronic Resource
    Electronic Resource
    Lack of interaction between disulfiram and alprazolam in alcoholic patients (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 157-160 
    Details
    ISSN: 1432-1041
    Keywords: alprazolam ; disulfiram ; drug interaction ; pharmacokinetics ; alcoholism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Certain interactions between disulfiram and benzodiazepines, especially diazepam and chlordiazepoxide, have previously been reported. The influence of disulfiram on the pharmacokinetics of alprazolam, a triazolobenzodiazepine, metabolized by hepatic microsomal oxidation, has been evaluated in 11 chronic alcoholic patients (6 males, 5 females) undergoing treatment for the alcohol withdrawal syndrome. Each patient received alprazolam 2 mg on the first day (control) followed by two weeks of treatment with disulfiram 0.5 g/d, and then further oral dose of alprazolam 2 mg. No significant change was found in any of the kinetic parameters. Thus, a therapeutic dose of disulfiram did not significantly alter the clearance or half-life of alprazolam in chronic alcoholic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265976
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  • 55
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of oral cyclosporin A in diabetic children and adolescents (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 181-184 
    Details
    ISSN: 1432-1041
    Keywords: cyclosporin A ; diabetic children ; pharmacokinetics ; dose adjustment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cyclosporin A (CsA) pharmacokinetics was studied in 19 diabetic children (mean age: 10.6 y). They were divided into prepubertal (I) and pubertal (II) groups according to plasma oestradiol or testosterone concentrations. The kinetic study was performed after a 72 h wash out period and a single oral dose of 7.5 mg/kg CsA. CsA in blood was measured by HPLC. The kinetic parameters: Cmax, tmax, t1/2, AUC, CL/f, Vz/f and tss were calculated. No significant difference was found between the two groups. A significant negative correlation was found between Vz and both total cholesterol (r=0.46), VLDL+LDL−cholesterol (r=−0.49) and VLDL+LDL−phospholipids (r=−0.58). CsA kinetics at steady-state were simulated by superimposition of single dose kinetics derived from each single dose. Measured steady-state blood concentrations were correlated (r=0.80) with the values predicted by the simulation. The results suggest that CsA adjustment dosage of the CsA may be performed after a single oral dose using blood levels measured by HPLC. This procedure requires validation in further studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265981
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    Pharmacokinetic interaction between cyclosporin and diltiazem (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 237-242 
    Details
    ISSN: 1432-1041
    Keywords: cyclosporin A ; diltiazem ; pharmacokinetics ; kidney transplantation ; drug metabolism ; cytochrome P-450 ; drug interactions ; human liver microsomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous reports have indicated that administration of the calcium antagonist diltiazem results in major changes in the pharmacokinetics of cyclosporin A (CyA). A new clinical trial was undertaken in 22 renal transplant patients receiving a constant dose of cyclosporin to further explore this interaction. Coadministration of diltiazem for one week produced an increase in the blood concentration of CyA and its metabolites 17 and 18 in almost all patients, but no increase in CyA metabolites 1 and 21. The mean whole blood CyA trough level determined by HPLC rose from 117 ng·ml−1 to 170 ng·ml−1 after one week on diltiazem, and the mean trough level of metabolite 17 rose similarly from 184 ng·ml−1 before to 336 ng·ml−1. Based on experiments with microsomes from human liver the effect of diltiazem was due to noncompetitve inhibition of CyA-metabolism by diltiazem, and the increased concentration of metabolite 17 might have been due to stronger inhibition of its secondary metabolism steps.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315023
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  • 57
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    Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 259-263 
    Details
    ISSN: 1432-1041
    Keywords: tacrine ; amyotrophic lateral sclerosis ; postoperative sedation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of 9-amino-1,2,3,4-tetrahydroacridine; tacrine, THA, was studied after intravenous administration and following the first and last oral doses of a seven week clinical trial involving 8 patients with amyotrophic lateral sclerosis, ALS. Two surgical patients given intravenous THA for reversal of postoperative sedation were also included. Plasma concentration of THA and in some cases the metabolite, 1-hydroxy-THA, were assayed using a selective and sensitive method with high performance liquid chromatography. After an intravenous dose of 30 mg THA, the plasma concentrations were fitted to a two-compartment model. Plasma clearance showed a threefold interindividual variation with a mean of 2.42 l·h−1. Volume of distribution, Vα varied 100–680 l with a mean of 349 l. The plasma half-lives of distribution and elimination were 1.8 and 98.2 min, respectively. Oral bioavailability showed large interindividual differences and ranged 6–36% in the four subjects studied. After seven weeks treatment with oral THA, plasma concentrations immediately prior to medication were below 10 ng/ml in three patients and above 100 ng/ml in two patients. At the same occasion the plasma metabolite concentrations considerably exceeded those of THA. THA medication was associated with side effects in the majority of the patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315027
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  • 58
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    Electronic Resource
    Pharmacokinetics of a valpromide isomer, valnoctamide, in healthy subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 289-291 
    Details
    ISSN: 1432-1041
    Keywords: valnoctamide ; valpromide ; valproic acid ; pharmacokinetics ; healthy subjects ; tranquiliser
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single 400 mg oral dose of valnoctamide (VCD) has been investigated in seven healthy, adult, male volunteers. VCD was not biotransformed rapidly to its corresponding acid valnoctic acid (VCA), unlike its isomer valpromide (VPD). It had a mean residence time of 13.2 h and a terminal half-life of 9.3 h. Throughout the study, only low plasma levels of VCA could be detected. Thus, unlike VPD, which is a prodrug of the corresponding acid, (valproic acid, VPA). VCD appears to act as a drug in its own right, and it does not undergo similar hydrolysis. The pharmacokinetic difference may account for the different pharmacological activities of the two isomers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315032
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  • 59
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    Electronic Resource
    Pharmacokinetics of intravenous diclofenac sodium in children (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 293-295 
    Details
    ISSN: 1432-1041
    Keywords: Diclofenac sodium ; children ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diclofenac sodium 0.5 mg/kg i. v. was given preoperatively to small children (age 4–6 y). Vt and total plasma clearance were higher than in adults but the elimination half-life was similar.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315034
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  • 60
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    Electronic Resource
    Pharmacokinetics of (+)-rolipram and (−)-rolipram in healthy volunteers (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 71-75 
    Details
    ISSN: 1432-1041
    Keywords: Rolipram ; enantiomers ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of S-(+)-rolipram and R-(−)-rolipram in six healthy male volunteers were measured by radioimmunoassay after intravenous injection of 0.1 mg and oral administration of 1.0 mg of the pure enantionmers. Following i.v. treatment, plasma levels of both isomers declined in three phases, with half-lives of 0.2 h, 0.6–0.9 h and 6–8 h. Total clearance was 6 ml · min−1 · kg−1. Oral administration of 1.0 mg gave a peak concentration of 16 ng · ml−1 after 0.5 h. Bioavailability of (+)-rolipram was 77% and of the (−) enantiomer it was 74%. There was no significant difference in Cmax, half-life, total clearance or bioavailability between the two enantiomers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314807
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  • 61
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    Electronic Resource
    The excretion of enalapril and enalaprilat in human breast milk (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 99-99 
    Details
    ISSN: 1432-1041
    Keywords: enalapril ; milk ; enalaprilat ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314815
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  • 62
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    Plasma levels of morphine and morphine glucuronides in the treatment of cancer pain: relationship to renal function and route of administration (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 121-124 
    Details
    ISSN: 1432-1041
    Keywords: morphine ; cancer ; morphine-6-glucuronide ; renal function ; drug metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary There is growing evidence that renally-impaired patients receiving morphine therapy are at greater risk of developing opiate toxicity, due to the accumulation of an active metabolite, morphine-6-glucuronide (M6G), which is usually excreted by the kidneys. This study examined the relationships between morphine dosage, renal function, and trough plasma concentrations of morphine and its glucuronide metabolites in 21 patients (aged mean: 68.5 years; 11 males) receiving either oral or subcutaneous morphine for terminal cancer pain. The median daily morphine dosages (mg · kg−1) were: orally 1.87 (range 0.37–6.82) and subcutaneously 1.64 (range 0.22–3.60). The median plasma concentrations of morphine, morphine-3-glucuronide (M3G), and M6G (ng · ml−1) were: 36.0, 1035.2, and 142.3, respectively. The plasma concentrations of morphine, M3G and M6G were each significantly related to the daily morphine dosage (n=21, Spearman r=0.79, 0.91, and 0.88 respectively). Accumulation of the morphine glucuronides was dependent on renal function. The plasma concentrations of M3G and M6G, when divided by the morphine concentration, were significantly related to the caluclated creatinine clearance of the patient. Patients receiving oral morphine had higher plasma concentration ratios of glucuronide/morphine than those receiving subcutaneous therapy, presumably due to first-pass glucuronidation. The results of this study confirm that accumulation of the pharmacologically active M6G is related to renal function, which probably explains the observation that morphine dosage requirements are generally reduced in patients with renal impairment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265969
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  • 63
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    Electronic Resource
    Influence of food on the bioavailability of metoprolol from an OROS system; a study in healthy volunteers (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 315-316 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; oral osmotic drug delivery system (OROS) ; food intake ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the bioavailability of metoprolol from an OROS system has been investigated. No significant difference was found between OROS administration to fasting subjects or after breakfast in any of the kinetic parameters (AUC, Cmax, tmax, C24 and lag time). Therefore, metoprolol OROS can be administered with breakfast.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315121
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  • 64
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    Electronic Resource
    Are all cardiac glycosides pharmacodynamically similar? (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 317-320 
    Details
    ISSN: 1432-1041
    Keywords: cardiac glycosides ; digitalis ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315402
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  • 65
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    Digoxin infusion versus bolus injection in rapid atrial fibrillation: relation between serum level and response (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 335-341 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; atrial fibrillation ; infusion ; pharmacokinetics ; simulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Using available data on time-concentration and time-effect relationships in normal persons the results of infusion of digoxin in various time periods were simulated and compared with administration of digoxin by bolus injections, using a three-compartment pharmacokinetic model to which a separate small side-effect compartment was subsequently added. The validity of the simulations was tested in 11 patients with rapid atrial fibrillation. Serum digoxin concentrations, ventricular rate and side effects were monitored in a double-blind study comparing an infusion of 1.5 mg digoxin over 6 h with administration of three bolus injections of 0.5 mg digoxin 8 h apart. In agreement with the predictions of the model, the maximal fall in ventricular rate was reached after 8–9 h in the infusion group and after 19–20 h in the bolus injection group, without any detectable difference in side effects. There were certain discrepancies between the results of the clinical study and the predictions of the model, e.g. in serum digoxin concentrations, perhaps due to impaired clearance in the patients. However, it is concluded that the tested model is valid in elderly patients with rapid atrial fibrillation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315571
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  • 66
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    Pharmacokinetics after a single oral dose of bopindolol in patients with cirrhosis (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 569-572 
    Details
    ISSN: 1432-1041
    Keywords: Bopindolol ; cirrhosis ; antipyrine ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration-time curve of the hydrolysis product of bopindolol has been investigated in 14 patients with cirrhosis and in 15 healthy volunteers given a single oral dose of 2 mg bopindolol. Cirrhosis was confirmed by history and clinical examination or liver biopsy. The time to maximum concentration, maximum concentration and AUC of hydrolyzed bopindolol were similar in the patients and controls. However, the elimination half-life was 6.0 h in controls and 9.5 h in cirrhotics. Antipyrine clearance was markedly decreased in patients with cirrhosis, but no correlation was found with the pharmacokinetic parameters of hydrolysed bopindolol. Although the AUC was not significantly altered in patients with cirrhosis, the longer half-life of hydrolysed bopindolol suggests impairment of its disposition in liver disease, which could lead to significant accumulation of drug during chronic dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316097
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  • 67
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    Electronic Resource
    A lack of pharmacokinetic interaction between ranitidine and piroxicam (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 583-586 
    Details
    ISSN: 1432-1041
    Keywords: ranitidine ; piroxicam ; interaction ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of piroxicam (40 mg) on the pharmacokinetics of ranitidine (150 mg) and of ranitidine (150 mg bid) on the pharmacokinetics of piroxicam (20 mg) were assessed in two 2-way crossover studies in two groups of 18 healthy male subjects. In the first study there were no statistically significant differences between the pharmacokinetic variables for ranitidine in the presence or absence of piroxicam. The mean maximum plasma concentration (Cmax) was 467 ng·ml−1 for ranitidine alone and 466 ng·ml−1 in the presence of piroxicam; mean area under the plasma concentration vs time curve (AUC) was 2460 h·ng ml−1 and 2551 h·ng ml−1 respectively; and the mean terminal half-life (t 1/2) was 3.6 h and 3.8 h respectively. In the second study there were no statistically significant differences between the pharmacokinetic variables for piroxicam in the presence or absence of ranitidine. The mean Cmax was 2.1 μ·ml−1 in the presence of placebo and 2.0 μg·ml−1 in the presence of ranitidine respectively; mean AUC was 133 h·μg ml−1 and 137 h·μg ml−1 respectively, and the mean t 1/2 was 53.6 h and 54.5 h respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316100
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  • 68
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    Comparison of the diuretic effect and absorption of a single dose of furosemide and free and the fixed combinations of furosemide and triamterene in healthy male adults (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 595-597 
    Details
    ISSN: 1432-1041
    Keywords: Furosemide ; triamterene ; drug combination ; absorption ; urine sodium ; urine potassium ; fixed combination ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption and diuretic effect of furosemide 40 mg alone (F), and of the free (F+T) and the fixed (FT) combinations of furosemide 40 mg and triamterene 50 mg have been compared in 12 healthy young men. A slight reduction in the area under the concentration-time curve (AUC) of plasma furosemide was found for the fixed combination (AUC480) F 2.58 μg · h · ml−1; F+T 2.46 μg · h · ml−1; FT 1.97 μg · h · ml−1. There was a significant reduction in the AUC480 of plasma triameterene (F+T 204.9 μg · h · l−1; FT 130.2 μg · h · l−1). Sodium excretion after F+T and FT was more pronounced than after F (F+T 302 mmol; FT 311 mmol; F 259 mmol). When compared to F alone, there was a reduction in the 24-hour potassium excretion after F+T as well as after FT (F 121 mmol; F+T 104 mmol; FT 107 mmol). It is concluded that the absorption of triamterene was significantly reduced after ingestion of the fixed combination tablet. However, in healthy male adults this had no influence on its natriuretic and potassium-sparing effect as compared to the free combination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316104
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  • 69
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    Electronic Resource
    Ivermectin binds avidly to plasma proteins (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 607-608 
    Details
    ISSN: 1432-1041
    Keywords: ivermectin ; pharmacokinetics ; plasma protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Human pharmacokinetic data on the new antiparasitic agent, ivermectin, are scanty. For the evaluation of its disposition a specific HPLC assay with sensitive fluorescence detection was developed. Applying equilibrium dialysis, plasma protein binding of ivermectin was measured in five healthy individuals and it averaged 93.2±4.4% (SD). Such strong binding should be taken into consideration, especially in patients with malnutrition or with diseases in which a decrease in plasma proteins and consequently a higher free fraction of ivermectin could be expected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316107
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  • 70
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    Electronic Resource
    Stereoselectivity of cholinesterase inhibition by galanthamine and tolerance in humans (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 603-605 
    Details
    ISSN: 1432-1041
    Keywords: Galanthamine ; Alzheimer's disease ; stereoselectivity ; cholinesterase inhibition ; side effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of galanthamine (GAL) and its 2 major metabolites on human cholinesterases has been explored. Epigalanthamine, a diastereomer of GAL, was 130-times less potent in vitro in its effect on acetylcholinesterase (AChE) in erythrocytes than the parent compound, and it did not differ significantly from the ketone galanthaminone. In vivo, the maximal 36–55% inhibition of AChE was approached 30 min after oral administration of 10 mg GAL. The duration of the catalytic inhibition corresponded to an elimination half-life of approximately 5–7 h. GAL was well tolerated in 8/8 healthy volunteers, and 3/4 Alzheimer patients tolerated the drug up to a daily dose of 40 mg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316106
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  • 71
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    Clinical implications of slow sulphoxidation of thioridazine in a poor metabolizer of the debrisoquine type (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 613-614 
    Details
    ISSN: 1432-1041
    Keywords: Thioridazine ; debrisoquine polymorphism ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316110
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  • 72
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    Effect of haemodialysis on the pharmacokinetics of cetirizine (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 67-69 
    Details
    ISSN: 1432-1041
    Keywords: Cetirizine ; haemodialysis ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Cetirizine, a histamine H1-receptor antagonist, were investigated in five renal failure patients undergoing chronic haemodialysis therapy. The patients received one 10 mg cetirizine dihydrochloride capsule 3 h before haemodialysis. Concentrations of cetirizine in serum and dialysate were determined by HPLC. The maximum serum cetirizine concentration and the time to reach that maximum were 285 μg·1−1 and 2.0 h, respectively. The terminal disposition half-life of cetirizine in these patients was 19.3 h. The haemodialysis clearance of cetirizine was 14.0 ml · min−1. Although this is approximately 33% of the apparent total body clearance of cetirizine in subjects with normal renal function, the fraction of the dose removed by dialysis was only 9.4%. Thus, since haemodialysis does not produce a clinically significantly alteration in cetirizine elimination, no supplemental dose should be necessary after dialysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314806
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  • 73
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    Pharmacokinetics of oral acetyl-L-carnitine in renal impairment (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 309-312 
    Details
    ISSN: 1432-1041
    Keywords: Acetyl-L-carnitine ; renal impairment ; pharmacokinetics ; adverse reactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetyl-L-carnitine 1.5 g and 3.0 g was administered as three divided doses on each of two occasions to 24 people with varying renal failure (creatinine clearance 127 – 8 ml·min−1). Plasma and urinary concentrations of total-L-carnitine, free (non-esterified) carnitine, short-chain esters and acetyl-L-carnitine were measured. The baseline (pre-study) concentrations of all four substances were related to renal function. Patients whose creatinine clearance was below about 30–40 ml·min−1 were had the highest concentrations. Renal elimination of all four substances was related to dose and to renal function. There was evidence for dose-related elimination, with greater elimination of the larger dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315038
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  • 74
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    Electronic Resource
    Plasma and cerebrospinal fluid concentrations of indomethacin in humans (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 343-346 
    Details
    ISSN: 1432-1041
    Keywords: indomethacin ; cerebrospinal fluid ; pharmacokinetics ; protein binding ; analgesic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and cerebrospinal fluid (CSF) concentrations of indomethacin have been determined in 52 patients hospitalized for nerve-root compression pain. Samples of blood and CSF were collected at the same time in each subject, 0.5 to 12 h after a single intramuscular injection of 50 mg indomethacin. Analgesic effect was assessed by the absolute and percentage variation in Huskisson's visual analogue scale between dosing and sampling. According to its high lipid solubility, indomethacin rapidly crossed the blood-brain barrier, being detected in CSF 0.5 h after administration. After attainment of equilibrium within 2 h, the CSF level exceeded the free plasma level. Since the drug was extensively bound to serum albumin (99.7±0.1%), this phenomenon may represent a slight degree of binding of indomethacin in CSF. The analgesic activity was not related to either the plasma or CSF concentration of indomethacin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315572
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  • 75
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    Biliary secretion of felodipine metabolites in man after intravenous [14C]felodipine (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 421-424 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; bile ; dihydropyridines ; biliary secretion ; healthy volunteers ; drug metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The biliary secretion of [14C]felodipine in 4 healthy human subjects was studied by use of the multiple marker dilution principle with double lumen tubes placed in the stomach and intestine. Insignificant amounts of14C activity were recovered from gastric aspirates. The individual recovery from intestinal aspirates varied from 2.9 to 8.5% of the dose of radioactivity over the period of 4.5 h after dosing. Less than 0.1% was identified as unchanged felodipine. The results show that biliary secretion is a minor route of elimination of felodipine or its metabolites. Bile collection for 4.5 h had no significant effect on the pharmacokinetics of felodipine, although the 72 h urinary recovery of radioactivity tended to be lower when bile was collected (59%) than in the control experiment (66%).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02336677
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  • 76
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    Pharmacokinetics of intravenous 2-mercaptopropionylglycine in man (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 499-503 
    Details
    ISSN: 1432-1041
    Keywords: 2-mercaptopropionylglycine ; body clearance ; half-life ; pharmacokinetics ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of 2-mercaptopropionylglycine (2-MPG) was studied in ten healthy volunteers after a single i. v. injection of 250 mg (1532 μmol). The total and non-protein-bound concentrations versus time curves were best described by a three-exponential function with terminal half-lives of 55 and 59 h respectively. Body clearance based upon the total concentration was estimated to be 105 and 231 ml/min based on the non-protein-bound 2-MPG. The corresponding values for Vss were 99 l and Vss,n 173 l, and for Vγ485 l and Vγ,n 1121 l respectively. 75% of the dose was excreted in the urine, mainly during the first 6 h after injection. The proportion of non-protein-bound 2-MPG diminished exponentially during the first 15 h and then levelled off at about 30%. There was a nonlinear increase in the non-protein-bound fraction of 2-MPG as the total plasma concentration of the drug increased.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02336691
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  • 77
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    Pharmacokinetics of emoxipine in normal animals and models of experimental pathology (1990)
    Springer
    Bulletin of experimental biology and medicine 110 (1990), S. 1372-1374 
    Details
    ISSN: 1573-8221
    Keywords: infarct ; stress ; pharmacokinetics ; emoxipine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00842289
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  • 78
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    Electronic Resource
    Pharmacokinetics of kemantane in rats (1990)
    Springer
    Bulletin of experimental biology and medicine 110 (1990), S. 1519-1521 
    Details
    ISSN: 1573-8221
    Keywords: kemantane ; immunostimulator ; pharmacokinetics ; active metabolite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00841308
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  • 79
    Electronic Resource
    Electronic Resource
    Introduction to toremifene (1990)
    Springer
    Breast cancer research and treatment 16 (1990), S. S 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; antitumor effects ; endocrine therapy ; estrogen receptor ; pharmacokinetics ; tamoxifen ; toremifene ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Toremifene, a triphenylethylene antiestrogen first synthesized in 1981, binds to the estrogen receptor with an affinity about 5% that of estradiol. Its antiestrogenicity/estrogenicity ratio in animal models is about 5 times that of tamoxifen, though it requires somewhat higher doses for full effectiveness, and it is active against breast cancer in animal and cell culture models. It has a long elimination half-life and there are several metabolites, but the principal antitumor activity appears to be due to the unchanged drug. In Phase I and Phase II clinical trials, toremifene has shown good response rates in ER-positive or ER-unknown tumors, and significant responses after failure of tamoxifen or other hormonal or chemotherapeutic regimens, with rare and mild side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01807138
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  • 80
    Electronic Resource
    Electronic Resource
    Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer (1990)
    Springer
    Breast cancer research and treatment 16 (1990), S. S 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; Phase I studies ; pharmacokinetics ; tolerance ; toremifene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%). Three patients with bone metastases from breast cancer developed hypercalcemia. At doses ≥40 mg/day a decline in LH and FSH occurred which was not statistically significant. At all doses tested SHBC rose during therapy. A dose dependent estrogenic blockade was seen on the vaginal epithelium following challenge with transdermal estradiol. Steady-state concentrations of toremifene were reached within 4 weeks, and at doses ≥60 mg/day ranged from 879-3445 ng/ml. The half-life was found to be 5 days, and at three weeks following discontinuation of treatment concentrations 〉24 ng/ml were detected. The N-desmethyl and 4-hydroxy metabolites achieved steady state levels within 4 weeks and had half-lives of 6 and 5 days respectively. Partial responses were seen in 4 patients, 3 with breast cancer treated at 200 mg/day and 1 with endometrial cancer treated at 400 mg/day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01807140
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  • 81
    Electronic Resource
    Electronic Resource
    Vasodilatory effects of nisoldipine on coronary arteries—Correlation with plasma levels (1990)
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 273-279 
    Details
    ISSN: 1573-7241
    Keywords: nisoldipine ; coronary vasomotility ; coronary stenoses ; pharmacokinetics ; dihydropyridine calcium antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vasomotion of angiographically normal and stenotic epicardial coronary arteries was analyzed up to 15 minutes after the onset of an intravenous infusion (4 minutes) of 0.5 mg (13 patients, group A) or 1 mg nisoldipine (13 patients, group B). After both doses the maximal increase of the mean diameters of normal coronary segments was achieved not before the 15th minute, averaging 11±6% in group A (p〈0.001) and 18±9% in group B (p〈0.001). Eleven of 15 and 8 of 9 coronary stenoses in groups A and B dilated to 5–80% and 15–70%, respectively. The nisoldipine concentration reached maximal levels at the end of the infusion (fourth minute) with an average of 8 ±4 ng/ml and 17±7 ng/ml in groups A and B, respectively. A significant correlation between nisoldipine plasma levels and dilation of normal coronary segments was obtained only with the individual maxima of these parameters and only in group A (p〈0.01). The hysteresis of the coronary dilation in relation to the drug plasma levels may be due to the high receptor affinity of nisoldipine. In either group nisoldipine provoked a persistent increase in coronary sinus oxygen sáturation (p〈0.01) and a substantial and prolonged drop in systolic and diastolic aortic pressure (p〈0.001). Both doses of nisoldipine induced a rise in heart rate (p〈0.01) and a slight drop in the rate-pressure product (p〈0.05).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01857645
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  • 82
    Electronic Resource
    Electronic Resource
    Minimal effective concentration values of propafenone and 5-hydroxy-propafenone in acute and chronic therapy (1990)
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 281-287 
    Details
    ISSN: 1573-7241
    Keywords: antiarrhythmic therapy ; pharmacokinetics ; propafenone ; ventricular premature beats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We evaluated the antiarrhythmic efficacy and the minimal effective concentrations of propafenone and its metabolite 5-hydroxy-propafenone during a) acute intravenous infusion (1.5 mg/kg in bolus followed by 45 minutes infusion), b) an acute oral single-dose test (450 mg), and c) 14-day chronic therapy (300 mg tid) followed by a washout. Oxidative metabolism was assessed by a debrisoquine oral test in every patient. Eleven patients with stable ventricular premature beats (VPBs)≥300/hr and Lown class ≥ 3 completed the study. The main results emphasized a certain discrepancy between the clinical effect of the acute intravenous infusion (efficacy in 5 out of 11 patients) and of the acute oral test and chronic therapy (efficacy in 11/11), with a time lag of the ECG changes during the acute intravenous infusion. The minimal effective concentrations were lower after acute oral administration compared with chronic treatment both for propafenone (200±189 ng/ml vs. 492±530 ng/ml; p〈0.05) and for 5-hydroxy-propafenone (82±40 ng/ml vs. 149±80 ng/ml; p〈0.02). A linear correlation was demonstrated between drug/metabolite ratios of propafenone and debrisoquine, either after acute oral (r=0.91) or after chronic administration (r=0.84). The pharmacokinetics of propafenone was nonlinear and showed wide interindividual variations. In conclusion, a) the lower efficacy and delayed electrophysiologic effects of propafenone after intravenous administration suggest that longer infusion times are necessary for complete antiarrhythmic efficacy; b) the differences observed in the minimal effective concentrations of acute versus chronic oral therapy suggest the development of partial tolerance to propafenone during chronic treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01857646
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  • 83
    Electronic Resource
    Electronic Resource
    A phase I study of toremifene (1990)
    Springer
    Breast cancer research and treatment 16 (1990), S. S 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; pharmacokinetics ; toremifene ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Phase I study of the new antiestrogenic drug toremifene was carried out in 27 Japanese women, using oral doses of 10–480 mg per day for one or five days. Serum concentrations reached a dose-dependent maximum 2–6 hours after each oral administration. Side effects were generally mild.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01807141
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  • 84
    Electronic Resource
    Electronic Resource
    Toremifene — panel discussion and summary (1990)
    Springer
    Breast cancer research and treatment 16 (1990), S. S 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; dose response ; multidrug resistance ; pharmacokinetics ; tamoxifen ; toremifene ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01807145
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  • 85
    Electronic Resource
    Electronic Resource
    Depressor effects and pharmacokinetics of single and consecutive doses of delapril in hypertensive patients with normal or impaired renal function (1990)
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 1417-1423 
    Details
    ISSN: 1573-7241
    Keywords: delapril ; ACE inhibitor ; depressor effect ; pharmacokinetics ; consecutive dose ; essential hypertension ; impaired renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The antihypertensive effects and pharmacokinetic properties of delapril, an angiotensin-converting enzyme (ACE) inhibitor, were investigated in hypertensive patients with normal renal function (NRF; n=6) and in those with impaired renal function (IRF; n=5). A 15-mg oral dose of delapril was given once on the first and last days, and twice daily on the other days. The measurement of blood pressure and sampling were done at 0, 1, 2, 4, 6, 12, and 24 hours postdose on the first and last days of treatment. Plasma and urinary concentrations of delapril and its metabolites were measured by HPLC. ACE activity was suppressed from 1 hour after the first dose to 24 hours after the last dose of delapril in both the NRF and IRF groups. During the consecutive dosing, significant BP falls were observed from 1 hour postdose of delapril to 24 hours in the NRF group and to 6 hours in the IRF group. Peak plasma concentrations of 5-hydroxydelapril diacid and areas under the plasma concentration-time curve (AUC) of both delapril diacid and 5-hydroxydelapril diacid in the IRF group were significantly higher (p〈0.001 or 0.05) than in the NRF group. No significant increase of pharmacokinetic parameters in repeated dosing was observed in both the NRF and IRF groups. Significant positive correlations (p〈0.001) were found between the inverse of creatinine clearance and the AUCs of the active diacid metabolites in single and consecutive doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02018270
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  • 86
    Electronic Resource
    Electronic Resource
    Could the increased antihypertensive efficacy of ketanserin in the elderly be due to altered pharmacokinetics? (1990)
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 89-92 
    Details
    ISSN: 1573-7241
    Keywords: ketanserin ; pharmacokinetics ; hospital ; general practice ; elderly hypertensive
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ketanserin is a serotonin S2-receptor antagonist that is an effective antihypertensive agent with a greater blood pressure reduction in older patients. We have reviewed the data from two studies of ketanserin pharmacokinetics in elderly patients, one in general practice (GP) and one in hospital patients. We compared these data with the results from two of our previous studies in young volunteers. The purpose was to determine whether the enhanced efficacy of ketanserin in elderly hypertensive patients could be due to altered pharmacokinetics. After a single dose of ketanserin, elderly hypertensives showed about a 60% increase in bioavailability compared with young volunteers. This increase is likely to be explained by a reduced metabolism of ketanserin on first pass through the liver. The elimination half-life of ketanserin was found to be longer in elderly hospital outpatients, but not in our elderly subjects in general practice. This prolongation of the elimination half-life of ketanserin appears to be unrelated to age, since the hospital outpatient elderly and elderly subjects in general practice were of similar ages. The elimination half-life of ketanserinol was longer in the hospital elderly subjects. This probably reflects a slight diminution of renal function in the elderly hospital outpatients, resulting in reduced clearance of ketaserinol. The peak and trough ketanserin concentrations were similar in young and elderly subjects during chronic treatment, and it is therefore unlikely that the increased efficacy of ketanserin in elderly patients is due to altered pharmacokinetcs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00053435
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  • 87
    Electronic Resource
    Electronic Resource
    Stability of plasma amiodarone levels during chronic oral therapy (1990)
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 529-530 
    Details
    ISSN: 1573-7241
    Keywords: amiodarone ; pharmacokinetics ; arrhythmias
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The variability of plasma amiodarone levels in 51 patients receiving chronic oral therapy over 4–53 (median 19) months was examined; 3–14 (median 5) plasma samples were obtained. After a loading dose, most patients received either 200mg or 400mg a day. Mean plasma amiodarone concentration was 1.2±0.6mg/l and mean plasma desethylamiodarone concentration, was 1.2±0.5mg/l. No relationship was seen between height and weight and plasma concentrations. Dose was a significant predictor of plasma level (p〈0.01) although it was a poor predictor of steady state amiodarone concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01857765
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  • 88
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and metabolism of fenbendazole in channel catfish (1990)
    Springer
    Veterinary research communications 14 (1990), S. 217-226 
    Details
    ISSN: 1573-7446
    Keywords: channel catfish ; fenbendazole ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fenbendazole (FBZ) was administered intravenously (1 mg/kg) and orally (5 mg/kg) to catheterized, confined channel catfish. Blood samples were collected for 72 h, and resulting FBZ plasma concentrations were pharmacokinetically modelled. Following intravenous administration t1/2α was 0.51 h, t1/2β was 16.8 h, body clearance (C1b) was 0.0598 L/kg/h, and Vd (area) was 1.45 L/kg. After oral administration the t1/2 (abs) was 1.47 h, the t1/2β was 20.1 h, and the tlag was 0.1 h. Following oral administration of 5 mg FBZ/kg body weight, the following tissues and body fluids were sampled for concentrations of FBZ, oxfendazole (FBZ-SO), sulphone metabolite (FBZ-SO2) and hydroxy metabolite (FBZ-OH): liver, posterior kidney, fat, muscle, bowel contents and urine. Fenbendazole was detected in the highest concentrations in abdominal fat, whereas oxfendazole was found primarily in the kidney, liver and abdominal fat. The sulphone metabolite was detected only in urine and bowel contents, while the hydroxy metabolite was found most often in the liver and abdominal fat samples.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00347741
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  • 89
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and distribution of ampicillin in plasma, milk and uterine fluid of female buffaloes (1990)
    Springer
    Veterinary research communications 14 (1990), S. 47-51 
    Details
    ISSN: 1573-7446
    Keywords: ampicillin ; buffalo ; milk ; pharmacokinetics ; plasma ; uterine fluid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A pharmacokinetic study of ampicillin (6 mg/kg intravenous) revealed that the peak concentrations of 17.81±1.25, 5.64±2.24 and 1.09±0.10 μg/ml of the drug were attained at 15 min, 30 min and 2 h in plasma, milk and uterine fluid respectively. A therapeutic concentration of ≥0.1 μg/ml was maintained from 15 min–8 h, 15 min–6 h and 30 min–6 h in plasma, milk and uterine fluid. Hence, the drug may be used effectively in mammary gland and uterine infections apart from its use in other systemic infections.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00346383
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  • 90
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and dosage regimen of cephalexin in buffalo calves (Bubalus bubalis) following single intravenous and intramuscular administration (1990)
    Springer
    Veterinary research communications 14 (1990), S. 59-62 
    Details
    ISSN: 1573-7446
    Keywords: buffalo ; cephalexin ; pharmacokinetics ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00346385
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  • 91
    Electronic Resource
    Electronic Resource
    A discriminatory study of a pharmacokinetic model for intramuscular gentamicin in sheep (1990)
    Springer
    Veterinary research communications 14 (1990), S. 53-58 
    Details
    ISSN: 1573-7446
    Keywords: gentamicin ; models ; pharmacokinetics ; sheep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The resulting serum concentrations were measured in six ewes after intramuscular administration of 10 mg/kg of gentamicin. The model providing the best fit for the experimental data was determined both by linear regression analysis between the experimental and theoretical values and by means of the Minimum Akaike Information Criterion Estimation (MAICE) test. Linear regression analysis showed certain differences favouring the monocompartmental model although the advantage was not conclusive. The MAICE test, however, permitted a clear discrimination in favour of the same model. When linear regression analysis is not conclusive, the MAICE test represents a good alternative.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00346384
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  • 92
    Electronic Resource
    Electronic Resource
    A comparison of some of the pharmacokinetic parameters of three commercial sulphadiazine/trimethoprim combined preparations given orally to pigs (1990)
    Springer
    Veterinary research communications 14 (1990), S. 403-410 
    Details
    ISSN: 1573-7446
    Keywords: combined preparations ; oral ; pharmacokinetics ; pig ; sulphadiazine ; trimethoprim
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three sulphadiazine/trimethoprim preparations were administered orally during feeding to pigs. Six male and six female pigs were used. Clinically important pharmacokinetic parameters of the two drugs in the three preparations were determined and compared. The plasma concentrations of sulphadiazine and trimethoprim increased rapidly in the pigs followed by a quite rapid decrease from 4 to 12 h after oral administration. The mean values of the absorption half-lives of sulphadiazine and trimethoprim were 0.9–1.6 h and 0.5–0.8 h, respectively. The corresponding values for the elimination half-lives of sulphadiazine and trimethoprim were 3.1–4.3 h and 3.4–6.0 h, respectively. There were no significant differences between the pharmacokinetic parameters of the two compounds in the three preparations with the exception of Tmax for sulphadiazine and t1/2β for trimethoprim. Comparative bioavailability calculations showed no statistically significant differences between sulphadiazine and trimethoprim in the three preparations. The weight increase of the pigs during the experimental period (mean = 37.3–64.9 kg) did not cause differences in the kinetics of the two drugs which could have consequences for the use of the three combined preparations in clinical practice. No unacceptable or antibacterial residues of sulphadiazine or trimethoprim were found in the kidneys of pigs slaughtered at 5, 7 and 10 days after administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00343218
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  • 93
    Electronic Resource
    Electronic Resource
    Stereoselective disposition of ibuprofen and flurbiprofen in rats (1990)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 2 (1990), S. 134-140 
    Details
    ISSN: 0899-0042
    Keywords: pharmacokinetics ; enantiomers ; 2-arylpropionates ; chiral inversion ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: (R)-2-Arylpropionates are often inverted to the pharmacologically active S-enantiomers in vivo, although there is significant interspecies variability in inversion. In order to provide a basis for determining the biochemical consequences of this unique process using rats as a model, it was important to establish the pharmacokinetic disposition of the enantiomers of ibuprofen, a drug well inverted in man and flurbiprofen, a drug apparently poorly inverted in man. Rats were dosed i.v. with a single dose of (R)-or (S)-ibuprofen (20 mg/kg), (R,S)-ibuprofen (40 mg/kg), (R)- or (S)-flurbiprofen (10 mg/kg), or (R,S)-flurbiprofen (20 mg/kg). Each treatment group consisted of six animals. Serial blood samples were withdrawn over a period of 6 h for ibuprofen and 10 h for flurbiprofen. These drugs were assayed in plasma by a stereospecific HPLC assay. The pharmacokinetics of the ibuprofen and flurbiprofen enantiomers were evaluated using a two-compartment open model with conversion of the R- to S-enantiomers in the central compartment. There was 50 ± 4% inversion of (R)-ibuprofen, a figure similar to that observed in man and (R)-ibuprofen had a higher clearance (12.6 ± 1.3 ml/min/kg) than (S)-ibuprofen (7.7 ± 0.7 ml/min/kg; P 〈 0.01). The clearance of (R)- flurbiprofen after racemate (2.3 ± 0.1 ml/min/kg) was higher than its clearance when administered alone (1.7 ± 0.2 ml/min/kg; P 〈 0.01), indicating a pharmacokinetic interaction between the enantiomers (most probably at plasma protein binding sites). A corresponding difference was not observed for ibuprofen. There was a small amount of inversion of (R)-flurbiprofen as determined by area analysis (4.5 ± 1.6%). However, this calculation may be in some error because of the interaction between the enantiomers. These data demonstrate quantitative similarities in the inversion of ibuprofen and flurbiprofen in rats and man, a useful basis for comparing the effects of these two drugs on fatty acid metabolism.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530020303
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  • 94
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    Electronic Resource
    Interindividual variability in the enantiomeric disposition of ibuprofen following the oral administration of the racemic drug to healthy volunteers (1990)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 2 (1990), S. 249-256 
    Details
    ISSN: 0899-0042
    Keywords: ibuprofen enantiomers ; R,S-ibuprofen ; enantiomer disposition ; pharmacokinetics ; human study ; interindividual variability ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The plasma disposition of the enantiomers of ibuprofen has been investigated following the oral administration of the racemic drug (400 mg) to 24 healthy male volunteers. The plasma elimination of (R)-ibuprofen was found to be more rapid than that of the S-enantiomer [plasma half-life: (R) 2.03 h; (S) 3.05 h; 2P 〈 0.001], resulting in a progressive enrichment in the plasma content of this isomer, some 64% of the total area under the plasma concentration time curves (AUC) being due to the pharmacologically active enantiomer. The influence of dose on the pharmacokinetic characteristics of the enantiomers of ibuprofen, over the range 200-800 mg, was investigated in three subjects. Examination of dosenormalized AUC values and oral clearance indicate the dose dependence of (R)-ibuprofen disposition.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530020410
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  • 95
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of the antitumor antibiotic n-pentyl-sparsomycin in beagle dogs (1990)
    Springer
    Investigational new drugs 8 (1990), S. 25-32 
    Details
    ISSN: 1573-0646
    Keywords: sparsomycin ; n-pentyl-sparsomycin ; pharmacokinetics ; beagle dogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary N-pentyl-sparsomycin (PSm) is a lipophilic analogue of sparsomycin (Sm), which is a well known inhibitor of protein synthesis. This compound was selected for preclinical pharmacokinetic studies because of its high in vitro and in vivo antitumor activity. In this study in which the drug was evaluated in beagle dogs under anaesthesia, the drug concentrations in plasma, urine and bile samples were determined using high performance liquid chromatography (HPLC). Plasma protein binding was approximately 54%. The mean t1/2 β was 0.2 hours (12 minutes) and t1/2 τ was 0.75 ± 0.1 hours (45 ± 6 minutes). During continuous infusions up to 5.25 hours, the steady state was reached in 3 out of 6 experiments, suggesting that in some cases the real t1/2 τ was longer than measured. PSm was actively reabsorbed from the renal tubuli. This process was saturable at the higher doses. Tubular reabsorption played only a minor role in pharmacokinetics as most of the drug (67%) was eliminated by the non-renal clearance. The non-renal clearance was saturable at higher doses of PSm and was the reason for non-linearity of pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216921
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  • 96
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    Electronic Resource
    In vivo and in vitro pharmacokinetics of 4,6-benzylidene-D-glucose (BG) in rats (1990)
    Springer
    Investigational new drugs 8 (1990), S. 149-157 
    Details
    ISSN: 1573-0646
    Keywords: benzylidene-glucosem ; BG ; HPLC ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In vivo pharmacokinetics of 4,6-benzylidene-D-glucose (BG) was investigated in rats following an i.v. bolus injection of 85 mg BG/kg body weight. High performance liquid chromatography (HPLC) was used to characterize and quantitate BG in whole blood or serum samples. It was found that BG rapidly disappeared with a half-life (t1/2)on the order of 10 min. At the same time a metabolite appeared which eluted before the double isomer peaks of BG. It increased in concentration from 0 to 30 min after initial i.v. injection of BG. Thereafter the metabolite was slowly removed or cleared from the animals. The t1/2 of the metabolite calculated from the time of maximum concentration was found to be about 1 h. BG was also metabolized by whole rat blood at 37°C, but on a different time scale in vitro. The t1/2 of BG in the in vitro assays was now about 4 h, as compared to 10 min in vivo. BG was not metabolized in rat plasma or rat serum. In contrast to in vivo data, the metabolite of BG was not reduced upon further incubation, but remained in blood samples with no reduction for at least 24 h. In addition, we found that protein synthesis was inhibited by approximately 50% when isolated rat hepatocytes were incubated with 3.2 mM BG. BG was slowly metabolized by hepatocytes to produce a metabolite indistinguishable (by HPLC) from that found in blood samples. Analysis of the metabolite by combined gas chromatography-mass spectrometric (GC-MS) methods identified it as being 1,3-benzylidene-D-glucitol. An intracellular reduction of BG by aldose reductase is proposed to occur.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177250
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  • 97
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    Electronic Resource
    Phase II trial of sequential methotrexate and 5-fluorouracil with leucovorin in children with sarcomas (1990)
    Springer
    Investigational new drugs 8 (1990), S. 181-182 
    Details
    ISSN: 1573-0646
    Keywords: methotrexate ; 5-fluorouracil ; leucovorin ; Ewing's sarcoma ; rhabdomyosarcoma ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177254
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  • 98
    Electronic Resource
    Electronic Resource
    A phase I and pharmacokinetic study of trimetrexate using a 24-hour continuous-infection schedule (1990)
    Springer
    Investigational new drugs 8 (1990), S. 159-166 
    Details
    ISSN: 1573-0646
    Keywords: antifolate ; phase I ; pharmacokinetics ; antimetabolite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limiting toxicity. Other toxicities included nausea and vomiting, stomatitis, erythema and phlebitis at the site of infusion, rash and skin hyperpigmentation, and elevated serum hepatic enzymes. Two drug-related deaths occurred secondary to leukopenia and sepsis. Twenty-six patients were evaluable for antitumor response. Twenty-one patients had progressive disease, while three patients had disease stabilization. There were two partial responses observed — one in a patient with breast cancer and a second in a patient with nasopharyngeal carcinoma. TMTX pharmacokinetics were studied in 15 patients. The drug had a mean terminal half-life of 13 hours. Steady-state was not achieved during the 24-hour infusions. Only 6% of the parent compound was excreted unchanged in the urine, and CSF levels averaged less than 2% of simultaneously measured plasma levels. A dose of 150 mg/m2 is recommended for phase II trials of TMTX using this 24-hour infusion schedule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177251
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  • 99
    Electronic Resource
    Electronic Resource
    A phase I and pharmacokinetic study of intravenous vinzolidine (1990)
    Springer
    Investigational new drugs 8 (1990), S. S51 
    Details
    ISSN: 1573-0646
    Keywords: vinzolidine ; phase I ; pharmacokinetics ; melanoma ; renal cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The semi-synthetic vinca alkaloid vinzolidine was administered to advanced cancer patients as an intravenous bolus on a three day schedule every 21 days. Forty-two patients were treated in this phase I trial. Five partial remissions (breast-1, melanoma-2, renal cancer-2) were seen in 30 evaluable patients. The dose limiting toxicities were myelosuppression and neuropathy. Erratic myelosuppression from course to course within the same patient as seen in previous trials with oral vinzolidine, was not observed with the intravenous formulation. The measured pharmacokinetic parameters conformed best to a 2-compartment model with a mean terminal half-life of 23 hours. The anti-tumor activity observed during this phase I trial and acceptable toxicity provide the basis for initiating phase II studies in selected forms of cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171984
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  • 100
    Electronic Resource
    Electronic Resource
    Comparison of methods to calculate cyclosporine a bioavailability from consecutive oral and intravenous doses (1990)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 18 (1990), S. 293-311 
    Details
    ISSN: 1573-8744
    Keywords: cyclosporine A ; pharmacokinetics ; bioavailability estimation ; plasma ; uremic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of cyclosporine A (CyA) was studied in 21 uremic patients. The plasma concentrations after an oral dose and a subsequent short-term infusion were analyzed simultaneously by nonlinear regression. Bi- and triexponential disposition models with either zero- or first-order absorption were fitted to the data. A triexponential disposition model with zero-order absorption was generally found to best describe the concentration-time profile. The bioavailability and clearance were estimated to be 0.24±0.10 and 21±8 L/hr, respectively. These values differed only marginally from those predicted by the other models. Similar bioavailability estimates were also obtained from a three-compartment model where elimination was assumed saturable, from a deconvolution procedure, and from analyses based on blood concentrations. Markedly higher bioavailabilities (0.34±0.13) were obtained when a model-independent AUCcorrection procedure, commonly used to calculate CyA bioavailability, was used. The difference could not be explained by poor description of data in the model-dependent analyses, but rather by overestimation in the model-independent analyses mainly due to errors in the extrapolations used. Thus, by the simultaneous fitting procedure, which is a new approach for estimating CyA bioavailability, drawbacks of the AUCcorrection procedure could be avoided. Further, future studies of CyA bioavailability could be designed with a markedly shorter and more convenient length of time if analyzed by the proposed method.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062270
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