Session: Poster Session: Human Pharmacokinetics/Dynamics
Monday, October 27, 2008: 12:00 AM
Room: Hall C
Background: The aim of this study was to investigate the potential drug-drug interaction between the novel antibiotic iclaprim and digoxin in healthy subjects. Methods: This was an open-label, randomised, two-period cross-over study in 14 healthy male subjects. A steady-state treatment regimen of oral digoxin 0.25 mg daily for 5 days was administered either alone or starting on day 3 concomitantly with an 11-days steady-state intravenous (IV) iclaprim treatment regimen. Treatment periods were separated by a washout period of at least 24 days. Plasma pharmacokinetics (PK) and urinary excretion of digoxin as well as PK of iclaprim were determined. Results: Systemic exposure of digoxin was determined after administration of the last dose of digoxin on day 5. Geometric mean ratio for the area under the plasma concentration - time curve (AUC0-∞) of digoxin (1.063) as well as the associated 90% confidence interval [CI: 0.952 - 1.187] were within the standard bioequivalence range. With regard to the maximum plasma concentration Cmax, the estimated ratio was 1.166 (90% CI: 0.974 - 1.396). The upper limit exceeded formally the accepted range of bioequivalence (0.80 - 1.25), but the minor increase in maximum plasma concentration during concomitant treatment with iclaprim was not clinically relevant. Renal clearance of digoxin was not affected by iclaprim (treatment ratio: 1.047 [90% CI: 0.880 - 1.245]). Administration of digoxin 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. Conclusions: Results of this study demonstrated that repeated IV infusions of iclaprim had no effect on the systemic exposure of orally administered digoxin investigated under steady-state conditions. Thus, IV infusions of iclaprim may be administered to patients on digoxin treatment without the necessity for dose adjustments of digoxin.