Population pharmacokinetics of phenytoin from routine clinical data in Japan.
Routine clinical pharmacokinetic data collected from out-patients who received phenytoin were analysed to estimate population pharmacokinetic parameters. There were 505 steady-state phenytoin concentrations and associated dosage rates (mg/day) from 220 out-patients. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data from many individuals. The influence of weight on the maximum elimination rate (Vm) and age on the Michaelis-Menten constant (Km) or the influence of dosage form on the bioavailability (F) of phenytoin were investigated. The Vm and Km of a 60-kg adult out-patient were estimated to be 369 mg/day and 3.67 mg/l, respectively. The parameter of a power function of weight was estimated to adjust Vm for body size. The best function adjusts Vm in proportion to weight to the 0.55 power. The Km for patients less than 15 years old was 16% less than that for adults. When the F of phenytoin is assumed to be 100% in the patients prescribed a tablet, the F value in the patients prescribed a powder was 89.5%.
Yukawa
E
E
Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Higuchi
S
S
Aoyama
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000493:pharmacokinetics*
D010672:Phenytoin