摘要:

AbstractThe percutaneous absorption of diclofenac was studied in ten healthy volunteers treated with Emulgel containing 1.16% diclofenac diethylammonium for 8 d as follows: a single application of 5 g Emulgel on days 1 and 8, and two applications d−1on days 2–7. Plasma concentration profiles of unchanged diclofenac and urinary concentrations of total diclofenac and metabolites (sum of free and conjugated) were determined.High inter‐individual variations in plasma and urine data were recorded, due probably to the permeability and the hydration of the skin. Steady state was reached after 2 d of twice‐daily administration. Plasma concentrations were low but remained in the range 10–50 nmol L−1over the full day for most of the subjects, indicating prolonged absorption from the appli

ISSN:0142-2782    

DOI:10.1002/bdd.2510150602

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY

摘要:

AbstractPotential effects of the coadministration of single doses of aspirin (325 mg) and of benazepril hydrochloride (20 mg) on the pharmacokinetics and the metabolism of these two drugs were evaluated in 12 healthy subjects. Plasma concentration profiles of benazepril, its active metabolite benazeprilat, and total salicylic acid were determined together with urinary excretion of benazeprilat, salicylic acid, salicyluric acid, and salicylate glucuronides. Almost superimposable plasma profiles of benazepril, benazeprilat, and total salicylic acid were achieved with the drugs given alone and concomitantly. The coadministration of benazepril hydrochloride and aspirin did not modify the pharmacokinetics or the metabolism of the two drugs.

ISSN:0142-2782    

DOI:10.1002/bdd.2510150603

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to determine whether a concomitant single oral dose of one of the anion exchange resins colestipol hydrochloride (10 g) or cholestyramine (8 g) administered with ibuprofen (400 mg) would alter the bioavailability of this non‐steroidal anti‐inflammatory agent. The study was performed according to a randomized three‐way crossover design in six healthy male volunteers. After dosing, serial blood samples were collected for a period of 10 h. Plasma harvested from blood was analysed for ibuprofen by a sensitive high‐performance liquid chromatographic method. There were no significant differences between colestipol treatment and control for peak plasma concentration (Cmax), time to peak concentration (Tmax), area under the plasma concentration—time curve (AUC), mean residence time (MRT), elimination rate constant (Kel), or elimination half‐life (t1/2). Cholestyramine treatment resulted in a significant decrease in AUC (26%,p<0.05) andCmax(34.4%,p<0.01) and a significant increase inTmax(80%,p<0.01) and MRT (20.2%,p<0.05). Cholestyramine administration showed no significant effect on theKelandt1/2values. A significant correlation was obtained between the increase in MRT and the increase inTmax. The confidence intervals (90%) of the mean values of the pharmacokinetic parameters (AUCO–∞andCmax) for the colestipol : control ratio were well within the acceptable range of 100 ± 20, whereas those for the cholestyramine : control ratio were outside it. Colestipol treatment was found to be bioequivalent to the control treatment by Schuirmann's two one‐sidedttests, while cholestyramine treatment was found to be bioinequivalent. The results indicate a lack of interaction between ibuprofen and colestipol and a potential significant interaction (decrease in rate and extent of absorption of ibuprofen) between cholestyramine and ibuprofen in patients receiving

ISSN:0142-2782    

DOI:10.1002/bdd.2510150604

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY

摘要:

AbstractVigabatrin (VGB), an irreversible inhibitor of GABA, is being developed as an add‐on therapy for uncontrolled complex partial seizure. A single‐dose study was conducted in three groups of subjects with normal, mild‐to‐moderate, and moderate‐to‐severe renal impairment to examine the effect of renal function on the pharmacokinetics of VGB. Serial blood samples were collected up to 60 h following a single 750 mg oral dose of VGB for the quantitation of drug concentrations. The plasma VGB concentration—time data were analyzed by mixed‐effects modeling to estimate population pharmacokinetic parameters and to identify any significant demographic covariates. The parameters of VGB were also calculated by standard two‐stage techniques and then compared to the results obtained using the mixed‐effects analysis. Population VGB plasma concentration—time profiles were best described by a two‐compartment model with zero‐order absorption. Creatinine clearance was observed to significantly affect the oral clearance of VGB (p<0.05), i.e. a linear increasing relationship existed between the two variables. Other demographic factors had no influence on VGB pharmacokinetics. There were agreements in the oral clearance, apparent volume of distribution during elimination, and half‐life estimates calculated by both methods. In addition, the conventional technique identified a linear relationship between oral and creatinine clearances. In summary, mixed‐effects modeling of serial vigabatrin data validated results determined by the

ISSN:0142-2782    

DOI:10.1002/bdd.2510150605

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY

摘要:

AbstractThe kinetics of amphotericin B (AMB) concentrations in plasma and interstitial fluid were studied in an experimental model ofCandida albicansinfection in rabbits. Rabbits were infected by subcutaneously implanted fibrin clots containing the yeast. Three groups of five rabbits received a 4 mg kg−1AMB infusion. AMB (Fungizone®) was dissolved in 5% glucose (group I) or in 20% Intralipid® at a final concentration of 1.5 (group II) or 3 mg mL−1(group III). AMB was measured by liquid chromatography in plasma and in trypsin‐dissolved fibrin clots up to 72 h after the infusion. No significant differences in AMB plasma and interstitial‐fluid concentration kinetics between the three modes of administration were found. AMB penetration into fibrin clots was slow, with no significant differences between treatments. Thus, formulation of AMB in Intralipid does not modify either the drug's interstitial or plasma kinetics at equival

ISSN:0142-2782    

DOI:10.1002/bdd.2510150606

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY

摘要:

AbstractFour controlled‐release nifedipine products were investigated in two clinical studies. In study 1, 22 healthy male volunteers took part in an open, multiple‐dose, randomized, crossover study to determine the relative bioavailablity of two 10 mg controlled‐release nifedipine tablet (Adalat® Retard, Bayer), administered 12 hourly, and one 20 mg controlled‐release nifedipine tablet (Adalat® Retard, Bayer) administered 12 hourly. In study 2, 24 healthy male volunteers took part in an open, multiple‐dose, randomized, three‐period, crossover study to determine the relative bioavailability of (i) two 30 mg nifedipine gastro‐intestinal therapeutic system (GITS) tablets (Adalat® XL, Bayer) administered once daily; (ii) one 60 mg nifedipine GITS tablet (Adalat® XL, Bayer) administered once daily; and (iii) one 20 mg plus one 10 mg nifedipine controlled‐release tablet (Adalat® Retard, Bayer), administered 12 hourly. In both studies detailed pharmacokinetic data, in particular with respect to the controlled‐release characteristics of the different formulations, were collected.Results of both studies indicate that all nifedipine products investigated are bioequivalent with respect to the extent of absorption of nifedipine. The nifedipine GITS products (Adalat® XL) have better controlled‐release properties than the Adalat® Retard product, and are suitable for

ISSN:0142-2782    

DOI:10.1002/bdd.2510150607

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY

摘要:

AbstractInter‐individual variations in the absorption lag time of pyridoxal phosphate were determined after administration of an enteric‐coated tablet (EC) or a plain capsule (PC) to 113 healthy volunteers under fasting, pre‐meal, and post‐meal conditions. The absorption lag time of pyridoxal phosphate was assessed from the urinary excretion of 4‐pyridoxic acid after administration of EC and PC. Significantly larger lag times after administration of both formulations were observed under post‐meal conditions than under pre‐meal conditions (0.477 ± 0.315 h versus 0.081 ± 0.086 h for PC and 1.995 ± 1.345 h versus 1.064 ± 1.327 h for EC), indicating that the mean gastric emptying rates of both a solution and a tablet were delayed after food intake. The lag time for PC showed little inter‐individual variation with (0–1.2 h) or without food (0–0. 25 h), whereas that for EC showed markedly large inter‐individual variation, from 0.25 to 2.63 h (median, 1.5 h) in the fasting condition, from 0.25 to>5.5 h (median 0.25 h) under pre‐meal conditions, and from 0.25 to>5.5 h (median 1.25 h) under post‐meal conditions. The effect of food on the gastric emptying rate of a solution appears to be almost uniform, whereas that for a tablet is so unpredictable that a reliable absorption rate for an enteric‐coated tablet cannot be expected, particularly unde

ISSN:0142-2782    

DOI:10.1002/bdd.2510150608

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY

摘要:

AbstractThe effect of food on the pharmacokinetics of the antiepileptic oxcarbazepine (OXC) was investigated in healthy volunteers. Six healthy male volunteers were treated with single peroral doses of 600 mg of oxcarbazepine (Trileptal®) after overnight fasting or a fat‐ and protein‐rich breakfast. Mean (± SD) areas under the plasma concentration—time curves (AUC) of the major component in plasma, the active monohydroxy metabolite (MHD), which is responsible for the therapeutic effect in man, were 672 (25) μmol L−1h when given to the fasted volunteers and 780 (31) μmol L−1h (p= 0.042) when given after a substantial breakfast. Mean (± SD) maximum concentrations (Cmax) were 25.5 (4.8) μmol L−1when given to the fasted volunteers and 31.4 (5.3) μmol L−1(p= 0.025) when given after breakfast. Thus, the average AUC was increased by 16% andCmaxby 23% when oxcarbazepine was given with food. The times at whichCmaxwas reached (tmax) as well as the terminal half‐lives were not influenced by concomitant intake of food. The tolerability was the same whether oxcarbazepine was given before or after food in healthy volunteers. The slight effect of food on the kinetics of oxcarbazepine should be of little t

ISSN:0142-2782    

DOI:10.1002/bdd.2510150609

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY

摘要:

AbstractDrugs that are largely restricted to the gastro‐intestinal tract (GIT) for their therapeutic efficacy and that are not substantially absorbed into the body are usually inadequately studied in terms of systemic bioavailability. The possibility of systemic effects requires that bioavailabilities be studied to ensure against enhanced toxicity resulting from formulation differences. Pyrantel pamoate falls into this category. High‐performance liquid chromatography was employed in this study to determine plasma levels of pyrantel in nine healthy human subjects after administration of tablet and suspension dosage forms. Mean peak plasma concentrations of 37.56 ± 9.37, 35.89 ± 8.94, and 36.22 ± 10.10 ng mL−1were obtained following administration of 750 mg pyrantel pamoate in three different formulations. The meantmaxvalues were 2.02 ± 0.12, 2.05 ± 0.356, and 2.05 ± 0.339 h respectively for the above dosage forms; the respective AUC0–9values were 81.01 ± 12.97, 94.59 ± 17.18, and 101.47 ± 19.59 h ng mL−1. There was no statistically significant difference between the bioavailabilities of the dosage forms tested. Large inter‐subject variations were observed. One subject experienced abdominal discomfort and one experienced dizziness. It was not possible to clearly correlate individual variations in absorption with the observed adverse effect because the number of incidents was low (two o

ISSN:0142-2782    

DOI:10.1002/bdd.2510150610

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510150601

出版商:John Wiley&Sons, Ltd.    

年代:1994

数据来源: WILEY