Effect of Clinafloxacin on the Pharmacokinetics of Theophylline and Caffeine

Abstract

Several quinolones are known inhibitors of cytochrome P450-1A2 mixed-function oxidase systems, causing decreased xanthine metabolism and higher than expected plasma concentrations. These higher concentrations become a serious consideration for the use of theophylline, a drug with a narrow therapeutic index. Both in vitro P450 induction/ inhibition and in vivo studies in the rat have suggested that clinafloxacin has a high potential for xanthine metabolic interaction in humans. Structure-activity relationships with other quinolones also suggest that clinafloxacin has a very high relative potential for xanthine interaction. Therefore, studies were conducted to evaluate the effect of multiple dose clinafloxacin administration on the single-dose pharmacokinetics of theophylline and caffeine.