Effect of quinolones on caffeine disposition

Clin Pharmacol Ther. 1989 Mar;45(3):234-40. doi: 10.1038/clpt.1989.23.


Six healthy volunteers received a single caffeine dose after pretreatment with norfloxacin, pipemidic acid, or placebo in a crossover, randomized, single-blind clinical trial. Quinolones altered the pharmacokinetics of caffeine, with a significant increase in the AUCs and a decrease in plasma clearance. The elimination half-life increased significantly with pipemidic acid. The apparent volume of distribution, mean renal clearance, and time to reach maximum caffeine concentrations remained unaltered. There was a decline in caffeine metabolite levels in the 24-hour urine samples for both quinolone treatments, suggesting that pipemidic acid and, to a lesser degree, norfloxacin inhibit metabolism of the N-demethylation pathways of caffeine. The practical consequence of this observation could be caffeine accumulation during repeated intake of coffee. In two additional healthy volunteers under a controlled multiple-dose regimen of caffeine ingestion, administration of pipemidic acid for 2 days caused a fourfold increase in the plasma concentrations of caffeine.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / pharmacology*
  • Caffeine / administration & dosage
  • Caffeine / metabolism
  • Caffeine / pharmacokinetics*
  • Drug Interactions
  • Humans
  • Male
  • Norfloxacin / pharmacology
  • Pipemidic Acid / pharmacology
  • Random Allocation


  • Anti-Infective Agents
  • Caffeine
  • Pipemidic Acid
  • Norfloxacin