NONMEM approach for estimating population pharmacokinetic parameters of phenytoin in Chinese epileptics
Rui, J.Z.; Cai, M.H.; Chu, X.M.; Chen, G.
Yao Xue Xue Bao 30(3): 172-178
1995
ISSN/ISBN: 0513-4870 PMID: 7639079 Document Number: 454779
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 cntdot 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 (V-m) and age on the Michaelis-Menten constant (K-m) were investigated. The V-m and K-m of phenytoin in a 60 kg adult out-patient, without combination with other drugs (phenobarbital, clonazepam or diazepam) were estimated to be 439 mg cntdot d-1 and 6.21 mu-g cntdot ml-1, respectively. The best function adjusts V-m to the 0.57 power in proportion to body weight. The K-m for patients less than 15 years old was 7% less than that for adults. The V-m of patients treated with phenytoin combined with phenobarbital, clonazepam or diazepam will increase 8.4 mg cntdot d-1.