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 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.
Kunii
Toshiki
T
Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan.
Fukasawa
Takashi
T
Yasui-Furukori
Norio
N
Aoshima
Toshiaki
T
Suzuki
Akihito
A
Tateishi
Tomonori
T
Inoue
Yoshimasa
Y
Otani
Koichi
K
D000328:Adult; D018592:Cross-Over Studies; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004311:Double-Blind Method; D004347:Drug Interactions; D015365:Enoxacin / Q000494:pharmacology*; D016666:Fluvoxamine / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D015365:Enoxacin; D019389:Cytochrome P-450 CYP2D6; D016666:Fluvoxamine