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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