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Fluvoxamine impairs single‐dose caffeine clearance without altering caffeine pharmacodynamics
Author(s) -
CulmMerdek Kerry E.,
Von Moltke Lisa L.,
Harmatz Jerold S.,
Greenblatt David J.
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02467.x
Subject(s) - fluvoxamine , caffeine , pharmacodynamics , placebo , crossover study , pharmacokinetics , pharmacology , sedation , anesthesia , medicine , fluoxetine , serotonin , receptor , alternative medicine , pathology
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.