Drug Interactions with Clinafloxacin

Author:

Randinitis Edward J.1,Alvey Christine W.1,Koup Jeffery R.1,Rausch George2,Abel Robert3,Bron Nicola J.2,Hounslow Neil J.2,Vassos Artemios B.2,Sedman Allen J.2

Affiliation:

1. Clinical Pharmacokinetics and Pharmacodynamics Department1,

2. Experimental Medicine Department2 and

3. Nonclinical Biostatistics Department,3Pfizer Global Research and Development, Ann Arbor, Michigan

Abstract

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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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