OBJECTIVE To estimate the pharmacokinete the parameter of valproic acid(VPA) and administration with individuation by
Bayesian and popular
pharmacokinetics parameter, and to optimize administration with individuation. METHODS 57 blood samples of VPA on steady-state trough level were collected from epileptic patients, who continuously po-administrated VPA for a long time. The serum concentrations and free drug concentration of all the samples were determined by
fluorescence polarization immunoassay(FPIA), respectively. Then individual pharmacokinetics parameters of VPA were estimated with Bayesian and popular pharmacokinetics parameters. And the influence of 18 factors such as sex, age etc on pharmacokinetics parameter and serum concentration was investigated through stepwise regression. Finally administration with individuation was optimized by the results and the therapeutic effect. RESULTS According to one-compartment open model with first-order absorption and elimination the individual pharmacokinetics parameters of VPA were worked out with Bayesian. The final result of individual pharmacokinetics parameter of VPA was CL =( 8.7 ± 0.6 ) mL·h -1 ·kg -1 ,The stepwise regression equation of CL was CL (mL·h -1 ·kg -1 )= 3.972 + 1.631 X_ 5 + 1.608 X_ 11 , The stepwise regression equation of C _ p0\} was: C _ p0\}(mg·L -1 )= 57.58 - 0.71 X_ 4 - 12.145 X_ 5 + 2.705 X_ 7 + 0.403 X_ 17 .In which X_ 4 was the body weight(kg), X_ 5 was ratio between the body height(cm) and the body weight(kg), X_ 7 was daily dose divided by body weight (mg·d -1 ·kg -1 ), X_ 11 was when VPA co-administrated with phenytoin coefficient 1 otherwise 0, X_ 17 was serum creatinine (μmol·L -1 ). There were no significant indifference between the average serum concentrations of VPA of epileptic patients estimated by Bayesian approach which was ( 53.5 ± 5.2 )mg·L -1 and the data actually assayed by FPIA which was ( 52.4 ± 5.4 )mg·L -1 , P > 0.05 . CONCLUSION Individual pharmacokinetics parameter of VPA can be estimated with Bayesian,and administration with individuation can be studied out and optimized by the Bayesian and the therapeutic effect.