Fluvoxamine impairs single‐dose caffeine clearance without altering caffeine pharmacodynamics
Year: 2005
Type: article
Abstract: 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.
Institutions: Tufts University, Tufts Medical Center
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: bronze
Awards: G1096835612, GARLIC PREPARATIONS AND ANTIRETROVIRAL DRUGS, G1554335716, G1555653344, G195712231, ANTIRETROVIRAL THERAPIES AND SUBSTANCE ABUSE, G2266918167, G3859415508, CHRONIC BENZODIAZEPINES: BEHAVIOR AND NEUROCHEMISTRY, CYP3A Function in Aging AfricanAmericans, REGULATION OF CYTOCHROME P4503A ACTIVITY IN THE ELDERLY, HAART Regimens in Substance Abusers, G763268302, G806220931, Metabolic Consequences of HAART: CYP3A and P-gp
OpenAlex ID: W2001737481