Interaction between sulthiame and clobazam: sulthiame inhibits the metabolism of clobazam, possibly via an action on CYP2C19.

The aim of this study was to investigate the effect of sulthiame (STM) on the pharmacokinetics of clobazam (CLB) by determining the concentration to dose (CD) ratio (serum level (ng/ml) divided by dose (mg/kg)) of CLB and that of N-desmethyl-clobazam (DMCLB). We evaluated five patients (an adult and four children) whose serum CLB and DMCLB concentrations were monitored after the addition or discontinuation of STM. Four of the five patients were CYP2C19 intermediate metabolizers, and one patient was an extensive metabolizer. When the patients were taking STM (100-275 mg/day), the mean CD ratio of DMCLB increased by 82.6 to 248.5%, which was higher than when they were not using STM. The increase was dose-dependent. In contrast, the CD ratio of CLB remained stable after addition or discontinuation of STM. These data suggest that STM has the potential to inhibit CYP2C19 enzyme activity. During combination therapy with STM and CLB in patients with CYP2C19 intermediate or extensive metabolizer phenotypes, monitoring of DMCLB concentrations may be helpful in ascertaining CLB-related adverse effects.