Interaction Study Between Enoxacin and Fluvoxamine

Abstract

Authors examined a possible interaction between enoxacin, an inhibitor of cytochrome P4501A2, and fluvoxamine (FLV), a substrate for this enzyme. Ten healthy male volunteers received enoxacin 200 mg/d or placebo for 11 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 Cmax (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.

In vitro inhibition of human cytochrome P450 by cudratricusxanthone A

“…The results of previous studies indicate that CTXA may alter the metabolism of CYP1A2. Enoxacin and fluvoxamine are strong inhibitors of CYP1A2, and their activities were previously reported in an in vivo drug-interaction, where enoxacin was an inhibitor of CYP1A2 and fluvoxamine was a substrate (Kunii et al, 2005). Decursin, used as a traditional Asian medicine for examining the pharmacokinetics of theophylline in rats, is a typical substrate of CYP1A2 enzyme (Chae et al, 2012).…”

Effects of Caffeine on the Kinetics of Fluvoxamine and its Major Metabolite in Plasma After a Single Oral Dose of the Drug

“…25 Therefore, the present results are almost in accordance with this pharmacokinetic principle, and suggest that caffeine slightly induces the metabolism of FLV. This induction is probably mediated by CYP1A2, because this enzyme is involved in FLV metabolism 5,6,8 and inducible by caffeine intake. 23,24 The specific metabolic pathway(s) of FLV induced by caffeine remains unclear, but the demethylation to FLA does not seem to be involved, because the pharmacokinetic parameters of FLA including the AUC-ratio of FLA to FLV were not significantly different between the 2 phases.…”

Quinolones

“…Scores from 0.5 to 4 h postdose were significantly higher (i.e. patients were more sleepy) during enoxacin coadministration compared with placebo coadministration (p < 0.05) [273]. A single-dose trial evaluating the effect of ciprofloxacin on sildenafil pharmacokinetics found that ciprofloxacin coadministration resulted in significant increases in t½ (mean 38%), AUC (mean 112%) and C max (mean 117%) (all p < 0.05).…”