title: Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics.
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.
  
  
  OBJECTIVE
  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.affiliation: Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts-New England Medical Center, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Culm-Merdek
authors.forename: Lisa L
authors.initials: LL
authors.lastname: von Moltke
authors.forename: Jerold S
authors.initials: JS
authors.lastname: Harmatz
authors.forename: David J
authors.initials: DJ
authors.lastname: Greenblatt
mesh_terms: D019540:Area Under Curve; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D016666:Fluvoxamine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
chemical_list: D002110:Caffeine; D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors