REDUCTION IN BLOOD-FREE CARNITINE LEVELS IN ASSOCIATION WITH CHANGES IN SODIUM VALPROATE (VPA) DISPOSITION IN EPILEPTIC PATIENTS TREATED WITH VPA AND OTHER ANTIEPILEPTIC DRUGS

Reduction in the blood free carnitine (FC) level as a side effect of s odium 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), phenyt oin (PHT) and/or carbamazepine (CBZ) in addition to VPA was significan tly lower than that in the controls given only these other anti-epilep tic 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 ot her 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 PC concentration and the L/D value of VPA were remarkably reduced in those patients receiving both medicatio ns, These results suggested that reduction in the blood FC level as a side effect of VPA reflected FC deficiency associated with the acceler ated degradation of VPA in liver; such a condition appears to result f rom medication with VPA and other AED(s) which induce(s) enzyme(s) for the VPA metabolism.