ISSN:0142-2782    

DOI:10.1002/bdd.2510120802

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe influence of concomitant food intake on plasma concentrations of the antidepressant drug fluvoxamine maleate was investigated in a two‐way, crossover study design. Eight male and four female healthy, young volunteers received a single oral dose of fluvoxamine maleate (50 mg, tablet) on two occasions: after an overnight fast and immediately after a breakfast. Food did not affect maximum fluvoxamine plasma levels (Cmax), or the time to reachCmax(tmax). The plasma AUC of fluvoxamine was on average 7 per cent lower in the fed than in the fasted state. It is concluded that the effect of food on the pharmacokinetics of fluvoxamine is negligibl

ISSN:0142-2782    

DOI:10.1002/bdd.2510120803

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractA comparative bioavailability study was conducted with two capsule formulations of danazol (200 mg) in 16 healthy adult male volunteers. Fasting subjects received single doses (400 mg) of each formulation on separate occasions 1 week apart. Blood samples were drawn at specified times up to 32 h after the dose and danazol concentrations in plasma were determined by a specific and sensitive HPLC method. The results for one subject were excluded as outlier values. The data from the other 15 subjects showed small differences, which did not achieve statistical significance between the formulations with respect toCmax,Tpeakand AUC0–∞. The mean elimination half‐life for danazol was 9·44 ± SD 2·74 h and the mean apparent total body clearance was 710 ± SD 2161 h−1. These data differed from previously published results, probably as a result of the more sensitive and specific assay method used in the present work. It is likely that a high proportion of the oral dose of danazol is eliminated by presystemic

ISSN:0142-2782    

DOI:10.1002/bdd.2510120804

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractA recently proposed method for bioavailability estimation, called the semi‐simultaneous method, was evaluatedin vivoin rats using methysergide as a test substance. In this method the test and the reference dose are administered with a short time interval and a model including the bioavailability parameters is fitted to the concentration‐time profile. In the present study, in order to control the true bioavailability, intravenous infusion was used to mimic extravascular administration and various input profiles were produced. Mono‐, bi‐ and triexponential disposition functions with the true and also various erroneous input models were fitted to the individual data sets. The models were also fitted to truncated data sets to mimic a situation where a long duration of sampling is precluded. A combined fitting‐deconvolution procedure was also applied. The simi‐simultaneous method gave precise and accurate estimates of the bioavailability in most groups and a robustness in the estimate concerning the model fitted was noted. The true input model could be identified for all data sets using common goodness‐of‐fit criteria. In the groups where a ‘flip‐flop’ situation was created (slower input than elimination) a poorer precision and accuracy and a higher sensitivity concerning the model fitted was observed. The model fitting and the fitting‐deconvolution procedure generally ga

ISSN:0142-2782    

DOI:10.1002/bdd.2510120805

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to determine the pharmacokinetics of acecainide (formerlyN‐acetylprocainamide) in six normal subjects of known acetylator phenotype. Three subjects were fast acetylators and three slow acetylators by sulfapyridine phenotyping criteria. Each subject received a 20‐min, 3 mg kg−1intravenous acecainide infusion. Concentrations of acecainide, procainamide, and their deethylated metabolites were measured in serum and urine samples using HPLC. Acecainide renal clearance, nonrenal clearance, steady‐state volume of distribution, and other pharmacokinetic parameters were estimated using standard approaches. Acecainide renal clearance and steady‐state volume of distribution were (mean ± SD) 13·6 ± 1·581 h−1and 135 ± 20·31, respectively, and were not significantly different in fast and slow acetylators. Acecainide nonrenal clearance in the six subjects was 3·0 ± 1·01 h−1, however, nonrenal clearance in slow acetylators was 1·8 times that in fast acetylators (3·9 vs 2·21 h−1,p= 0·012) with clear separation of the subjects into two groups when the data were grouped by acetylator phenotype. The nonrenal clearance of acecainide was inversely correlated with percentage sulfapyridine acetylation. Computer simulations were conducted to explore possible explanations for the observed diff

ISSN:0142-2782    

DOI:10.1002/bdd.2510120806

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of ambenonium, a reversible cholinesterase inhibitor, in rats was investigated following intravenous administration of the drug. Mean residence time and steady state volume of distribution were 23–36 min and 0·20–0·311 kg−1, respectively, and were dose independent at the dose of 0·3–3 μmole kg−1. Total body clearance of 8·2 ml min−1kg−1over 0·3 μmole kg−1was slightly increased to 11·3 ml min−1kg−1at 3 μmole kg−1. Renal clearance was also increased with the increase of the dose, while hepatobiliary clearance was substantially constant. Ambenonium was highly concentrated in the liver, kidney, spleen, and lung. About 30 per cent of the dose is concentrically stored in the liver at 6 h after administration, and

ISSN:0142-2782    

DOI:10.1002/bdd.2510120807

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe effects of age on the pharmacokinetics of pentisomide (CM7857), an orally effective antiarrhythmic agent, were studied in two groups of volunteers. Sixteen young volunteers (mean age 26·4 years) and 10 elderly volunteers (mean age 67·8 years) received a single 200 mg oral dose of pentisomide. Mean AUC was larger and terminal elimination half‐life longer in the elderly subjects, due to a decrease in total plasma clearance of pentisomide in the elderly. This decrease was due to a reduction in renal clearance of the drug which was paralleled by a significantly lower creatinine clearance in the elderly subjects. Dosage reduction, or a reduced frequency of dosing of pentisomide would be necessary in the elderly or those with impaired renal funct

ISSN:0142-2782    

DOI:10.1002/bdd.2510120808

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510120809

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510120801

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY