Reduction in Blood Free Carnitine Levels in Association with Changes in Sodium Valproate (VPA) Disposition in Epileptic Patients Treated with VPA and Other Anti-epileptic Drugs

摘要

Reduction in the blood free carnitinc (FC) level us a side effect of sodium valproate {VPA) given epileptic patients was pharmncokincticnlly studied in connection with changes in the VPA disposition. The scrum FC level in patients taking at least one of phcnobarbital (PB), phenytoin (PUT) and/or carbamazepine (CBZ) in addition to VPA was significantly lower than that in the controls given only these other anti-cpilcptic 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 I'C 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 AF.D(s) which inducc(.s) enzyme(s) for the VPA metabolism.