持続性バルプロ酸錠剤使用小児患者における血中バルプロ酸濃度解析 Ｐｏｐｕｌａｔｉｏｎ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃ Ｐａｒａｍｅｔｅｒｓの推定

Abstract

The population pharmacokinetic parameters of valproic acid in pediatric patients taking tablets (Depakene® R) which were designed to be long acting were estimated using the standard two-stage method. On this study, the patients comprised seven pediatric outpatients of our hospital, aged 8 to 12 years old, all of whom were in the steady-state level. Blood samples were collected just before administration and six times thereafter until 30 h. The pharmacokinetic parameters were calculated by utilizing a one-compartment model with first-order absorption after a lag time by using the Phaconet-Depakene® program.Although the estimated population pharmacokinetic parameters, apparent elimination rate constant (Ke, h-1), apparent volume of distribution (Vd, 1/kg) and apparent absorption lag time (Lag, h) of pediatric patients did not differ from those of adult healthy volunteers reported previously, apparent absorption rate constant (Ka, h-1) was significantly smaller than that of adults. Prediction of the maximum and minimum concentration with the Bayesian method using these estimated parameters and one-point serum concentration data showed that the prediction error was less than 10%. At the steady state, the concentration of serum valproic acid decreased until 2.9h after administration. It is noteworthy important that the esrum concentration level about 3 hours after administration of Depakene® R did not indicate the maximum concentration but rather the minimum concentration.In conclusion, the estimated population pharmacokinetic parameters of valproic acid in pediatric patients taking Depakene® R were determined for the Bayesian analysis by Phaconet-Depakene®.