Interaction study between fluvoxamine and quazepam

It has been reported that fluvoxamine, an inhibitor of various cytochrome P450 enzymes, markedly inhibits the metabolism of several drugs. The purpose of the present study was to examine a possible interaction between fluvoxamine and quazepam. Twelve healthy male volunteers received fluvoxamine 50 mg/day or placebo for 14 days in a double-blind randomized crossover manner, and on the 4th day they received a single oral 20-mg dose of quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 hours after quazepam dosing. Plasma concentrations of quazepam and its active metabolites 2-oxoquazepam (OQ) and N-desalkyl-2-oxoquazepam (DOQ) were measured by high-performance liquid chromatography (HPLC). Fluvoxamine did not change plasma concentrations of quazepam but significantly decreased those of OQ from 6 to 12 hours and those of DOQ from 3 to 48 hours. The AUC ratio of OQ to quazepam was significantly lower in the fluvoxamine phase. Fluvoxamine did not affect psychomotor function at most of the time points. The present study suggests that fluvoxamine slightly inhibits the metabolism of quazepam to OQ, but this interaction appears to have minimal clinical significance.