The effect of cimetidine on the single dose pharmacokinetics of oral clobazam and N‐desmethylclobazam

The effect of cimetidine on the single dose pharmacokinetics of orally administered clobazam and N‐desmethylclobazam (NDMC) was studied in volunteers. Cimetidine inhibited the elimination of both clobazam and NDMC and inhibited the rate of formation of NDMC from clobazam. The increase in the AUC for NDMC generated from clobazam was relatively greater than that for clobazam itself. This suggests that NDMC elimination is inhibited to a relatively greater extent than clobazam elimination. The increase in AUC for NDMC generated from clobazam was also relatively greater than that for NDMC administered orally. This would suggest that cimetidine either increases the bioavailability of clobazam or reduces that of NDMC. The increases in the AUC for NDMC and for clobazam in some individuals was of a magnitude which is likely to be clinically significant.