Hiraoka A, Arato T, Tominaga I
Kyorin University School of Health Sciences, Hachioji-shi, Tokyo, Japan.
Biol Pharm Bull. 1997 Jan;20(1):91-3. doi: 10.1248/bpb.20.91.
Reduction in the blood free carnitine (FC) level as a side effect of sodium valproate (VPA) given epileptic patients was pharmacokinetically studied in connection with changes in the VPA disposition. The serum FC level in patients taking at least one of phenobarbital (PB), phenytoin (PHT) and/or carbamazepine (CBZ) in addition to VPA was significantly lower than that in the controls given only these other anti-epileptic drugs (AEDs). Patients medicated only with VPA also tended to have a lower serum FC level than the controls, although the difference was not significant. Among all the patients taking VPA with or without other AED(s), a significantly positive correlation was observed between the serum FC level and the value of dose and level ratio (L/D) of VPA, indicating that both the serum FC concentration and the L/D value of VPA were remarkably reduced in those patients receiving both medications. These results suggested that reduction in the blood FC level as a side effect of VPA reflected FC deficiency associated with the accelerated degradation of VPA in liver; such a condition appears to result from medication with VPA and other AED(s) which induce(s) enzyme(s) for the VPA metabolism.
针对癫痫患者服用丙戊酸钠（VPA）导致血游离肉碱（FC）水平降低这一副作用，结合VPA处置变化进行了药代动力学研究。除VPA外还至少服用苯巴比妥（PB）、苯妥英（PHT）和/或卡马西平（CBZ）其中之一的患者血清FC水平显著低于仅服用这些其他抗癫痫药物（AEDs）的对照组。仅服用VPA的患者血清FC水平也往往低于对照组，尽管差异不显著。在所有服用或未服用其他AEDs的VPA患者中，血清FC水平与VPA的剂量与血药浓度比值（L/D）之间存在显著正相关，表明在同时服用这两种药物的患者中，血清FC浓度和VPA的L/D值均显著降低。这些结果表明，VPA副作用导致的血FC水平降低反映了与肝脏中VPA加速降解相关的FC缺乏；这种情况似乎是由服用VPA和其他诱导VPA代谢酶的AEDs引起的。
