首页   按字顺浏览 期刊浏览 卷期浏览 Steady-state Pharmacokinetics of Phenytoin from Routinely Collected Patient Data†
Steady-state Pharmacokinetics of Phenytoin from Routinely Collected Patient Data†

 

作者: T. H. Grasela,   L. B. Sheiner,   B. Rambeck,   H. E. Boenigk,   A. Dunlop,   P. W. Mullen,   J. Wadsworth,   A. Richens,   T. Ishizaki,   K. Chiba,   H. Miura,   K. Minagawa,   P. G. Blain,   J. C. Mucklow,   C. T. Bacon,   M. Rawlins,  

 

期刊: Clinical Pharmacokinetics  (ADIS Available online 1983)
卷期: Volume 8, issue 4  

页码: 355-364

 

ISSN:0312-5963

 

年代: 1983

 

出版商: ADIS

 

数据来源: ADIS

 

摘要:

Previously reported routine phenytoin clinical pharmacokinetic data from Japan, England, and Germany were analysed to estimate population pharmacokinetic parameters. There were 780 steady-state phenytoin concentrations and associated dosage rates (mg/day) from 322 patients. The patient group spanned paediatric and adult ages, mean age being 18.4 ± 17.3 (SD) years; 53% were males. The data were analysed using NONMEM, a computer programme designed for population pharmacokinetic analysis. Estimates of the influence of age, gender, data source, height and weight on the maximum elimination rate (Vm) and Michaelis-Menten constant (Km) were obtained. The Vm and Km of a 70kg adult male European were estimated to be 415 mg/day and 5.7 mg/L, respectively. Vm is not influenced by gender, age or data source. The parameters of a power function of height and weight were estimated to adjust Vm for body size. The best function adjusts Vm in proportion to weight to the 0.6 power; height contains no useful information.Km is not influenced by gender. The Km for patients less than 15 years old is 43% less than that of older patients. The Km of Japanese patients appears to be 23% less than that for European patients.Even after adjustments for age, etc., apparent Vm and Km vary unpredictably among individuals with a coefficient of variation between 10 to 20%, and approximately 50% respectively.

 

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