Sugiyama Ikuo, Bouillon Thomas, Yamaguchi Masayuki, Suzuki Hikoe, Hirota Takashi, Fink Martin
Drug Metabolism and Pharmacokinetics, Novartis Pharma K.K., Tokyo, Japan; Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
Integrated Quantitative Sciences, Novartis Pharma AG, Basel, Switzerland.
Drug Metab Pharmacokinet. 2015 Apr;30(2):160-7. doi: 10.1016/j.dmpk.2014.12.002. Epub 2014 Dec 10.
Oxcarbazepine is an anti-epileptic drug, which is almost completely metabolized by cytosolic enzymes in the liver to the active 10-monohyroxy metabolite (MHD) following oral administration. The pharmacokinetic (PK) profiles of MHD were evaluated in pediatric epileptic patients and a possible ethnic difference in PK of MHD between Japanese and non-Japanese pediatric patients was assessed. A non-linear mixed effect modeling approach was used to determine the PK of MHD. A one-compartment population model with first-order absorption appropriately described the PK of MHD. No clinically relevant differences were found for using body surface area or weight to explain between-patient variability, therefore the final model included the effects of body weight on apparent clearance (CL/F) and apparent volume of distribution (V/F) of MHD, and in addition, the effect of 3 concomitant anti-epileptic drugs (carbamazepine, phenobarbital and phenytoin) on CL/F of MHD. Inclusion of ethnicity as a covariate in the final model, concluded no ethnic difference with respect to CL/F of MHD between Japanese and non-Japanese patients. Hence, oxcarbazepine can be generally applied using the same dosage and administration for the treatment of partial onset seizures in pediatric patients, regardless of ethnicity.
奥卡西平是一种抗癫痫药物，口服给药后，它几乎完全由肝脏中的胞质酶代谢为活性代谢物10-单羟基代谢物（MHD）。在小儿癫痫患者中评估了MHD的药代动力学（PK）特征，并评估了日本和非日本小儿患者之间MHD的PK可能存在的种族差异。采用非线性混合效应建模方法来确定MHD的PK。具有一级吸收的单室群体模型能恰当描述MHD的PK。在使用体表面积或体重来解释患者间变异性方面未发现临床相关差异，因此最终模型纳入了体重对MHD的表观清除率（CL/F）和表观分布容积（V/F）的影响，此外，还纳入了3种联合使用的抗癫痫药物（卡马西平、苯巴比妥和苯妥英）对MHD的CL/F的影响。在最终模型中纳入种族作为协变量后，得出日本和非日本患者之间在MHD的CL/F方面不存在种族差异的结论。因此，无论种族如何，奥卡西平通常都可以使用相同的剂量和给药方式来治疗小儿患者部分性发作。
