Interaction study between enoxacin and fluvoxamine

Authors examined a possible interaction between enoxacin, an inhibitor of cytochrome P4501A2, and fluvoxamine (FLV), a substrate for this enzyme. Ten healthy mate volunteers received enoxacin 200 mg/d or placebo for I I days in a double-blind randomized crossover manner, and on the eighth day they received a single oral 50-mg dose of FLV. Blood samplings and pharmacodynamic evaluation were conducted up to 72 hours after FLV dosing. Plasma concentrations of FLV and its active metabolite fluvoxamino acid (FLA) were measured by high-performance liquid chromatography. Enoxacin significantly increased the plasma concentrations at 2 hours (placebo versus enoxacin, mean SD: 4.4 +/- 2.4 vs 7.0 +/- 4.1 ng/mL, P < 0.05) and 3 hours (7.4 +/- 2.7 vs 11.2 +/- 3.8 ng/mL, P < 0.01) and the C-max (10.2 +/- 2.9 vs 11.6 +/- 4.0 ng/mL, P < 0.05) of FLV. Plasma concentration and pharmacokinetic parameters of FLA were not affected by enoxacin. Enoxacin significantly (P < 0.05) increased the scores of the Stanford Sleepiness Scale from 0.5 to 4 hours, suggesting that enoxacin increased the sleepiness produced by FLV. The present study suggests that enoxacin slightly inhibits the metabolism of FLV and enoxacin should be combined with FLV with caution.