¹AstraZeneca R&D Mölndal, AstraZeneca LP, Mölndal, Sweden

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 (C_max) for amoxicillin and doxycycline. For ciprofloxacin, the 90% CI fell within the no-interaction range for AUC, but the lower limit for C_max was slightly outside this range (0.68 versus 0.70) on Days 1 and 5. The mean time to C_max, 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.