Effect of quinolones on caffeine disposition

• Published in: Clinical pharmacology and therapeutics Vol. 45; no. 3; p. 234
• Main Authors: Carbó, M, Segura, J, De la Torre, R, Badenas, J M, Camí, J
• Format: Journal Article
• Language: English
• Published: United States 01.03.1989
• Subjects: 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
• ISSN: 0009-9236
• 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.