Lack of effect of the novel antibiotic iclaprim on the anticoagulant activity and the pharmacokinetics of warfarin in healthy subjects

Abstract number: P549

Zeman P., Trenk D., Cap M., Leggewie S., Stengele E., Hadvary P., Islam K.

Objectives: The aim of this study was to investigate the potential drug-drug interaction between the novel antibiotic iclaprim and the anticoagulant drug warfarin in healthy subjects.

Methods: This was an open-label, randomised, two-period cross-over study in twelve healthy male subjects. Administration of either a single oral dose of warfarin 25 mg alone (W) or a single oral dose of warfarin 25 mg on day three of an eight-day steady-state intravenous (IV) iclaprim treatment regimen (W+I) was performed. The treatment periods were separated by a washout period of at least 12 days. Plasma pharmacokinetics (PK) of R, S-warfarin and the anticoagulant activity of warfarin (INR – International Normalised Ratio) as well as PK of iclaprim were determined. Safety parameters of the warfarin and the iclaprim plus warfarin treatment regimens were assessed in addition.

Results: Total anticoagulant effect of warfarin was determined by calculation of the area under the effect vs. time curve; treatment ratio of W/W+I (AUEC: 1.059 [1.004, 1.116] 90% confidence interval) and the maximum INR observed (1.077 [1.020, 1.137]) were close to unity. Therefore, the anticoagulant activity of warfarin was not affected by concomitant treatment with iclaprim. Ratios for the area under the plasma concentration time curve (AUC0-infinity) of the more potent S-enantiomer of warfarin (1.009 [0.949, 1.074]) and the maximum plasma concentration (Cmax: 1.005 [0.947, 1.066]) were within the conventional bioequivalence ranges. Similar findings were obtained with regard to PK parameters of R-Warfarin which confirms lack of interaction between iclaprim and warfarin. Administration of warfarin during the course of iclaprim treatment had no effect on plasma PK of iclaprim determined after the first infusion as well as during steady-state of the antibiotic. Administrations of iclaprim and warfarin were well-tolerated by the study subjects.

Conclusions: Results from this study demonstrated that repeated intravenous infusions of iclaprim had no effect on the anticoagulant activity and plasma pharmacokinetics of orally administered warfarin. Thus, IV infusions of iclaprim may be administered to patients on warfarin treatment without the necessity for dose adjustments of the anticoagulant drug.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Location: Barcelona, Spain
Presentation type:
Back to top