Effect of quinolones on caffeine disposition.
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.
Carbó
M
M
Department of Pharmacology and Toxicology, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
Segura
J
J
De la Torre
R
R
Badenas
J M
JM
Camí
J
J
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002110:Caffeine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009643:Norfloxacin / Q000494:pharmacology; D010876:Pipemidic Acid / Q000494:pharmacology; D011897:Random Allocation
D000890:Anti-Infective Agents; D002110:Caffeine; D010876:Pipemidic Acid; D009643:Norfloxacin