Effects of caffeine on the kinetics of fluvoxamine and its major metabolite in plasma after a single oral dose of the drug.
The effects of caffeine on the kinetics of fluvoxamine (FLV) and its major metabolite fluvoxamino acid (FLA) in plasma, after a single oral dose of the drug, were studied in 12 healthy male volunteers. The subjects received caffeine 300 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 sampling and pharmacodynamic evaluation were conducted up to 72 hours after FLV dosing. Plasma concentrations of FLV and FLA were measured by high-performance liquid chromatography. Caffeine significantly decreased the plasma concentrations at 6 time points (P<0.05) and total area under the plasma concentration-time curve (156.5+/-51.7 vs. 118.9+/-38.2 ng/h/mL, P<0.01) of FLV. Plasma concentration and pharmacokinetic parameters of FLA were not affected by caffeine. Caffeine induced no significant change in the pharmacodynamic effects of FLV. The present study suggests that caffeine slightly induces the metabolism of FLV, probably mediated by CYP1A2.
Fukasawa
Takashi
T
Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan. tfukasaw@med.id.yamagata-u.ac.jp
Yasui-Furukori
Norio
N
Suzuki
Akihito
A
Ishii
Genki
G
Inoue
Yoshimasa
Y
Tateishi
Tomonori
T
Otani
Koichi
K
D000328:Adult; D000596:Amino Acids / Q000097:blood; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002110:Caffeine / Q000494:pharmacology*; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004311:Double-Blind Method; D016666:Fluvoxamine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate
D000596:Amino Acids; D018687:Antidepressive Agents, Second-Generation; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D016666:Fluvoxamine; C477448:fluvoxamino acid