Major influence of CYP2C19 genotype on the steady-state concentration of N~desmethylclobazam

摘要

N-desmethylclobazam (N-CLB), the major metabolite of clobazam (CLB), exerts a large influence on the therapeutic and adverse effects of CLB. A substantial inter-individual variability has been observed in the ratios of N-CLB concentration / CLB dose and of the N-CLB / CLB concentration. Such variability in the ratios has been partly attributed to concurrent medication [1, 2], especially in those patients receiving drugs that induces CYP3A4 (phenobarbital, carbamazepine, and phenytoin [3]). CYP3A4 is the major isoenzyme of the cytochrome P450 (CYP) enzyme family which is pivotal in biotransformation of diverse drugs. CYP3A4 metabolizes CLB to N-CLB leading to the increased serum N-CLB / CLB concentration ratio. However, in patients who are not receiving CYP3A4 inducers, the serum N-CLB concentration is still not predictable from the initial CLB dose alone.