Pharmacokinetics of ciprofloxacin in the rat and its interaction with cyclosporin A: a microdialysis study Original Research Article

Ciprofloxacin is a broad spectrum fluoroquinolone antibacterial agent. In order to investigate the effect of cyclosporin A on the pharmacokinetics of ciprofloxacin in rats, a technique using blood microdialysis coupled to liquid chromatography was employed in this study. Microdialysis probe was inserted into the jugular vein/right atrium of male Sprague–Dawley rat for sampling of a protein unbound drug. The pharmacokinetics between i.v. doses of 20 or 50 mg/kg ciprofloxacin were compared with those treated with a single i.v. dose of 20 mg/kg cyclosporin A prior to the ciprofloxacin administrations. This study showed that a single dose treatment with cyclosporin A resulted in a significant increase in the pharmacokinetic parameters estimated for the higher dose of ciprofloxacin (50 mg/kg) but no significant difference at the lower dose of ciprofloxacin (20 mg/kg). The results suggest that cyclosporin A alters the pharmacokinetics of ciprofloxacin in rats. Possible mechanisms for this interaction include the blocking by cyclosporin A of the protein binding of ciprofloxacin with P-glycoprotein in rat blood.