[NONMEM approach for estimating population pharmacokinetic parameters of phenytoin in Chinese epileptics].
Routine clinical pharmacokinetic data collected from epileptic out-patients who received phenytoin (PHT) were analysed to estimate population pharmacokinetic parameters. There were 258 steady-state serum phenytoin concentrations and associated dosage (mg.d-1) from 161 out-patients. The data were analysed using NONMEM program. The influence of body weight, drug combinations and sex on the maximum elimination rate (Vm) and age on the Michaelis-Menten constant (Km) were investigated. The Vm and Km of phenytoin in a 60 kg adult out-patient, without combination with other drugs (phenobarbital, clonazepam or diazepam) were estimated to be 439 mg.d-1 and 6.21 micrograms.ml-1, respectively. The best function adjusts Vm to the 0.57 power in proportion to body weight. The Km for patients less than 15 years old was 7% less than that for adults. The Vm of patients treated with phenytoin combined with phenobarbital, clonazepam or diazepam will increase 8.4 mg.d-1.
Rui
J Z
JZ
Department of Clinical Pharmacology, General Hospital of Nanjing Armed Forces.
Cai
M H
MH
Chu
X M
XM
Chen
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010672:Phenytoin / Q000493:pharmacokinetics*
D010672:Phenytoin