NONMEM APPROACH FOR ESTIMATING POPULATION PHARMACOKINETIC PARAMETERS OF PHENYTOIN IN CHINESE EPILEPTICC

Routine clinical pharmacok inetic data collected from epileptic out-patients whoreceived phenytoin(PHT)were analysed to estimate population pharmacokinetic parameters.Therewere 258 steady-state serum phenytoin concentrations and associated dosage (mg·d^-1)from 161out-patients.The data were analysed using NONMEM program.The influence of body weight,drugcombinations and sex on the maximum elimination rate(V_m)and age on the Michaelis-Mentenconstant(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·d^-1 and 6.21μg· ml^-1,respectively. The best function adjusts V_m to the 0.57 power in proportion to body weight.The K_m forpatients less than 15 years old was 7%less than that for adults. The V_m of patients treated withphenytoin combined with phenobarbital ,clonazepam or diazepam will increase 8.4 mg·d^-1.