Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics
Culm-Merdek KE, von Moltke LL, Harmatz JS, Greenblatt DJ
British journal of clinical pharmacology · 40 citas
Cómo se estudió
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- Financiación
- Financiación independiente
- Gobierno
- National Institutes of Health
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- National Institute on Aging
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- National Institute of Mental Health
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- National Institute on Drug Abuse
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- National Institute of Diabetes and Digestive and Kidney Diseases
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- National Center for Complementary and Integrative Health
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- NCCIH NIH HHS
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- Subvenciones
- National Institute on Aging (AG-17880); National Institute of Mental Health (R01 MH058435); National Institutes of Health (RA-00054); National Institute on Drug Abuse (DA 13834); National Institute of Mental Health (MH 58435); National Institute on Drug Abuse (R21DA013209); National Center for Complementary and Integrative Health (AT01381); National Center for Complementary and Integrative Health (R01 AT001381); National Institute of Diabetes and Digestive and Kidney Diseases (DK-58496); National Institute on Aging (R01AG017880); National Institute on Drug Abuse (R01 DA013834); National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK058496); National Institute on Drug Abuse (R01 DA005258); National Institute on Drug Abuse (DA 13209); National Institute on Drug Abuse (DA05258)
Según 12 financiadores declarados.
Publicación
- Publicado
- 2005-07-27 · Br J Clin Pharmacol · vol. 60 · número 5 · págs. 486–493
- Editorial
- Wiley
- Citado
- 58 citas · más que el 76% de estudios similares · 1.0× el promedio de su campo
- Referencias
- 34 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Pharmacogenetics and Drug Metabolism · Coffee research and impacts · Forensic Toxicology and Drug Analysis
- Palabras clave
- fluvoxamine, caffeine, drug-drug interactions, CYP1A2 inhibition, caffeine clearance, elimination half-life, psychomotor performance, EEG beta activity, central nervous system stimulation
- MeSH
- humans, fluvoxamine, caffeine, central nervous system stimulants, drug combinations, electroencephalography, chromatography, high pressure liquid, area under curve, cross-over studies, double-blind method, psychomotor performance, drug interactions, half-life, middle aged, female, male, selective serotonin reuptake inhibitors
4 autores
- Kerry Culm-Merdek🇺🇸Tufts University; Tufts Medical Center
- Lisa Lvon Moltke🇺🇸Tufts University; Tufts Medical Center
- Jerold S. Harmatz🇺🇸Tufts University; Tufts Medical Center
- David J. Greenblatt🇺🇸 · autor de correspondenciaTufts University; Tufts Medical Center
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
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