Stiripentol Changes Serum Concentration of Desmethylclobazam -Four Cases with CYP2C19 Polymorphism-

Abstract

Stiripentol (STP; unapproved in Japan), a drug for severe myoclonic epilepsy in infancy (SMEI), is a strong inhibitor of cytochrome P450 (CYP) 2C19. We compared the level-to-dose-ratio (LDR) of desmethylclobazam (DCLB) derived from clobazam concomitantly used with STP to that without STP in two cases of homozygous extensive metabolizer (hmEM), one case of heterozygous EM (htEM) and one case of poor metabolizer (PM). In two hmEM cases, the LDR was 11 times and 1.7 times higher when combined with STP than without, respectively. In a htEM case, the LDR was 4.8 times higher with STP. In a PM case, the LDR with STP decreased to 60% compared with that without STP; the inhibitory effect was not observed. Because CYP2C19 is involved in the metabolism of several drugs including antiepileptic drugs and also because the ratio of PM in Japanese is as high as 20%, it is recommended to determine CYP2C19 polymorphism beforehand in order to predict possible interactions when using STP.