title: Drug interactions with clinafloxacin.
abstract: Many fluoroquinolone antibiotics are inhibitors of cytochrome P450 enzyme systems and may produce potentially important drug interactions when administered with other drugs. Studies were conducted to determine the effect of clinafloxacin on the pharmacokinetics of theophylline, caffeine, warfarin, and phenytoin, as well as the effect of phenytoin on the pharmacokinetics of clinafloxacin. Concomitant administration of 200 or 400 mg of clinafloxacin reduces mean theophylline clearance by approximately 50 and 70%, respectively, and reduces mean caffeine clearance by 84%. (R)-Warfarin concentrations in plasma during clinafloxacin administration are 32% higher and (S)-warfarin concentrations do not change during clinafloxacin treatment. An observed late pharmacodynamic effect was most likely due to gut flora changes. Phenytoin has no effect on clinafloxacin pharmacokinetics, while phenytoin clearance is 15% lower during clinafloxacin administration.
authors.affiliation: Clinical Pharmacokinetics and Pharmacodynamics Department, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA. Edward.Randinitis@pfizer.com
authors.forename: E J
authors.initials: EJ
authors.lastname: Randinitis
authors.forename: C W
authors.initials: CW
authors.lastname: Alvey
authors.forename: J R
authors.initials: JR
authors.lastname: Koup
authors.forename: G
authors.initials: G
authors.lastname: Rausch
authors.forename: R
authors.initials: R
authors.lastname: Abel
authors.forename: N J
authors.initials: NJ
authors.lastname: Bron
authors.forename: N J
authors.initials: NJ
authors.lastname: Hounslow
authors.forename: A B
authors.initials: AB
authors.lastname: Vassos
authors.forename: A J
authors.initials: AJ
authors.lastname: Sedman
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*; D014859:Warfarin / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D000927:Anticonvulsants; D065607:Cytochrome P-450 Enzyme Inhibitors; D024841:Fluoroquinolones; D002110:Caffeine; D014859:Warfarin; D010672:Phenytoin; C057477:clinafloxacin; D013806:Theophylline