A-1894. The Novel Antibiotic Iclaprim Had No Effect on the Steady-State Pharmacokinetics of Digoxin in Healthy Subjects
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.
Stefan Leggewie, MD1, Dietmar Trenk2, Eberhard Stengele, MD, PhD1, Khalid Islam, PhD3, Meike Cap, MD1, Paul Zeman, PhD4, Paul Hadváry, PhD3 and  P. Hadvary,
Arpida Ltd. Role(s): Employee, Received: Salary., (1)Herz-Zentrum Bad Krozingen, (2)Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany, (3)Arpida AG, Reinach, Switzerland, (4)Arpida Ltd.