BACKGROUND: Coadministration of fluvoxamine impairs the clearance of caffeine and prolongs its elimination half-life, which is attributable to inhibition of CYP1A2 by fluvoxamine. The clinical importance of this interaction is not established. AIM: To evaluate the effects of fluvoxamine on the kinetics and dynamics of single doses of caffeine. METHODS:Seven healthy subjects received single 250 mg doses of caffeine (or matching placebo) together with fluvoxamine (four doses of 100 mg over 2 days) or with matching placebo in a double-blind, four-way crossover study. For 24 h after caffeine or placebo administration, plasma caffeine and fluvoxamine concentrations were determined. Psychomotor performance, sedation, and electroencephalographic (EEG) "beta" frequency activity were also assessed. RESULTS:Fluvoxamine significantly reduced apparent oral clearance of caffeine (105 vs. 9.1 mL min(-1), P < 0.01; mean difference: 95.7 mL min(-1), 95% CI: 54.9-135.6), and prolonged its elimination half-life (4.9 vs. 56 h, P < 0.01; mean difference: 51 h, 95% CI: 26-76). Caffeine produced CNS-stimulating effects compared with placebo. However, psychomotor performance, alertness, or EEG effects attributable to caffeine were not augmented by coadministration of fluvoxamine. CONCLUSIONS:Fluvoxamine greatly impaired caffeine clearance, but without detectable changes in caffeine pharmacodynamics. However, this study does not rule out possible adverse effects due to extensive accumulation of caffeine with daily ingestion in fluvoxamine-treated individuals.
RCT Entities:
BACKGROUND: Coadministration of fluvoxamine impairs the clearance of caffeine and prolongs its elimination half-life, which is attributable to inhibition of CYP1A2 by fluvoxamine. The clinical importance of this interaction is not established. AIM: To evaluate the effects of fluvoxamine on the kinetics and dynamics of single doses of caffeine. METHODS: Seven healthy subjects received single 250 mg doses of caffeine (or matching placebo) together with fluvoxamine (four doses of 100 mg over 2 days) or with matching placebo in a double-blind, four-way crossover study. For 24 h after caffeine or placebo administration, plasma caffeine and fluvoxamine concentrations were determined. Psychomotor performance, sedation, and electroencephalographic (EEG) "beta" frequency activity were also assessed. RESULTS:Fluvoxamine significantly reduced apparent oral clearance of caffeine (105 vs. 9.1 mL min(-1), P < 0.01; mean difference: 95.7 mL min(-1), 95% CI: 54.9-135.6), and prolonged its elimination half-life (4.9 vs. 56 h, P < 0.01; mean difference: 51 h, 95% CI: 26-76). Caffeine produced CNS-stimulating effects compared with placebo. However, psychomotor performance, alertness, or EEG effects attributable to caffeine were not augmented by coadministration of fluvoxamine. CONCLUSIONS:Fluvoxamine greatly impaired caffeine clearance, but without detectable changes in caffeine pharmacodynamics. However, this study does not rule out possible adverse effects due to extensive accumulation of caffeine with daily ingestion in fluvoxamine-treated individuals.
Authors: L L von Moltke; D J Greenblatt; S X Duan; J S Harmatz; C E Wright; R I Shader Journal: J Clin Psychopharmacol Date: 1996-04 Impact factor: 3.153
Authors: L L von Moltke; D J Greenblatt; J S Harmatz; S X Duan; L M Harrel; M M Cotreau-Bibbo; G A Pritchard; C E Wright; R I Shader Journal: J Pharmacol Exp Ther Date: 1996-02 Impact factor: 4.030
Authors: Chuanhai Cao; David A Loewenstein; Xiaoyang Lin; Chi Zhang; Li Wang; Ranjan Duara; Yougui Wu; Alessandra Giannini; Ge Bai; Jianfeng Cai; Maria Greig; Elizabeth Schofield; Raj Ashok; Brent Small; Huntington Potter; Gary W Arendash Journal: J Alzheimers Dis Date: 2012 Impact factor: 4.472
Authors: Oliver von Richter; Gezim Lahu; Andreas Huennemeyer; Rolf Herzog; Karl Zech; Robert Hermann Journal: Clin Pharmacokinet Date: 2007 Impact factor: 6.447
Authors: M Bosilkovska; C F Samer; J Déglon; M Rebsamen; C Staub; P Dayer; B Walder; J A Desmeules; Y Daali Journal: Clin Pharmacol Ther Date: 2014-04-10 Impact factor: 6.875