title: 4-quinolones inhibit biotransformation of caffeine.
abstract: The pharmacokinetics of caffeine, including formation of its major metabolite paraxanthine in plasma, has been investigated in 12 healthy males (age 20-40 years) alone and during co-administration of the 4-quinolones ofloxacin, norfloxacin, pipemidic acid, ciprofloxacin, and enoxacin; ciprofloxacin and enoxacin were given in 3 different dose levels. The naphthyridine derivative enoxacin and the pyrido-pyrimidine derivative pipemidic acid had caused marked inhibition of caffeine and paraxanthine metabolism, whereas the genuine quinolone derivatives norfloxacin and ciprofloxacin had little effect, and the pyrido-benzoxacine derivative ofloxacin had no detectable effect. The different molecular and spatial structures of the compounds appear to be responsible for the differences in inhibitory potency.
authors.affiliation: Department of Clinical Pharmacology, University Hospital, Frankfurt/Main, Federal Republic of Germany.
authors.forename: S
authors.initials: S
authors.lastname: Harder
authors.forename: A H
authors.initials: AH
authors.lastname: Staib
authors.forename: C
authors.initials: C
authors.lastname: Beer
authors.forename: A
authors.initials: A
authors.lastname: Papenburg
authors.forename: W
authors.initials: W
authors.lastname: Stille
authors.forename: P M
authors.initials: PM
authors.lastname: Shah
mesh_terms: D000328:Adult; D001711:Biotransformation / Q000187:drug effects; D002110:Caffeine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015365:Enoxacin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009643:Norfloxacin / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D010876:Pipemidic Acid / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology*; D011897:Random Allocation; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D015363:Quinolones; D015365:Enoxacin; D002110:Caffeine; D002939:Ciprofloxacin; D015242:Ofloxacin; D013806:Theophylline; D010876:Pipemidic Acid; D009643:Norfloxacin; C021183:1,7-dimethylxanthine