Pharmacokinetic interaction on valproic acid and recurrence of epileptic seizures during chemotherapy in an epileptic patient

Abstract

To report a pharmacokinetic interaction between valproic acid (VPA) and anticancer agents observed in an epileptic patient. A 34-year old male epileptic patient receiving VPA underwent cisplatin-based chemotherapy for the treatment of a testicular tumour. The first chemotherapeutic cycle decreased the serum VPA concentration and caused severe generalized tonic-clonic seizures. Thus, thereafter, the serum VPA concentration was monitored along with the chemotherapy. In a patient receiving VPA daily, severe seizures were observed 7 weeks after the first chemotherapeutic cycle, at which the serum VPA concentration was found to be reduced by approximately 50% of the initial level (90-100 microg ml(-1)). The following cycles (six cycles over a 7-month period) also caused seizures in association with decreased serum VPA concentrations. In contrast, the serum concentration of phenytoin, which was given daily after the second chemotherapeutic cycle, remained at a therapeutic concentration (10-20 microg ml(-1)). After the completion of chemotherapy, the serum concentration of a tumour marker, hCGbeta, decreased to 1.2 ng ml(-1) from more than 120 ng ml(-1) prior to the chemotherapy in this patient. Careful monitoring of VPA concentrations are necessary during cisplatin-based chemotherapy because anticancer agents can reduce the serum concentration and antiepileptic activity of VPA.