Pharmacokinetic interaction on valproic acid and recurrence of epileptic seizures during chemotherapy in an epileptic patient.
OBJECTIVE
To report a pharmacokinetic interaction between valproic acid (VPA) and anticancer agents observed in an epileptic patient.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Careful monitoring of VPA concentrations are necessary during cisplatin-based chemotherapy because anticancer agents can reduce the serum concentration and antiepileptic activity of VPA.
Ikeda
Hiroaki
H
Department of Pharmaceutical Services, Hiroshima University Hospital, Minami-ku, Hiroshima 734-8551, Japan. ike@hiroshima-u.ac.jp
Murakami
Teruo
T
Takano
Mikihisa
M
Usui
Tsuguru
T
Kihira
Kenji
K
D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004347:Drug Interactions; D004827:Epilepsy / Q000139:chemically induced*; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D012008:Recurrence; D013736:Testicular Neoplasms / Q000188:drug therapy*; D014635:Valproic Acid / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D001761:Bleomycin; D014635:Valproic Acid; D005047:Etoposide; D002945:Cisplatin