No effect of amoxicillin, doxycycline, and ciprofloxacin on the pharmacokinetics and pharmacodynamics of ximelagatran

Abstract

Background The effects of amoxicillin, doxycycline, and ciprofloxacin on the pharmacokinetics and pharmacodynamics of melagatran after administration of oral ximelagatran were evaluated. Methods Healthy volunteers (n=48) sequentially received two treatments: ximelagatran 36 mg as a single oral dose and, after a ≥2-day washout period, amoxicillin, doxycycline, or ciprofloxacin for Days 1 to 5 with a 36-mg dose of ximelagatran on Days 1 and 5. Results The 90% confidence interval (CI) and least squares mean estimates for ximelagatran with:without the antibiotic as a single dose (Day 1) and at steady-state (Day 5) fell within the range demonstrating no interaction for area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax) for amoxicillin and doxycycline. For ciprofloxacin, the 90% CI fell within the no-interaction range for AUC, but the lower limit for Cmax was slightly outside this range (0.68 versus 0.70) on Days 1 and 5. The mean time to Cmax, half-life, and renal clearance of melagatran did not differ as a function of whether ximelagatran was given with an antibiotic. None of the antibiotics affected melagatran-dependent prolongation of activated partial thromboplastin time. Co-administration of ximelagatran with the antibiotics was well tolerated. Conclusion The pharmacokinetics, pharmacodynamics, and tolerability of oral ximelagatran were not affected by amoxicillin, doxycycline, or ciprofloxacin. Clinical Pharmacology & Therapeutics (2005) 77, P46–P46; doi: 10.1016/j.clpt.2004.12.069