PI‐71

BACKGROUND/AIMS To investigate the potential pharmacokinetic (PK)/pharmacodynamic (PD) interaction between digoxin and rotigaptide, a first‐in‐class cardiomyocyte gap junction modifier, in healthy subjects. METHODS In this open‐label, nonrandomized, three‐period study, 15 male subjects received a single 24‐h IV infusion of rotigaptide 10 mg/day on day 1, followed by loading oral doses of digoxin 0.5 mg bid on day 2 and 0.25 mg bid on day 3, followed by daily maintenance dose of 0.25 mg for a total of 11 days. The last three doses of digoxin were administered concomitantly with a 3‐day continuous IV infusion of rotigaptide 10 mg/day. Plasma and urine PK parameters of rotigaptide and digoxin were estimated. A bioequivalence testing approach was adopted to detect the potential PK interaction between the combination and monotherapy. RESULTS Co‐administration of digoxin with rotigaptide did not alter the steady‐state PK of digoxin. The 90% confidence intervals for combination to monotherapy ratios of the geometric means of C max and AUC SS of digoxin fell within the window of 80% to 125%. Likewise, digoxin did not alter the single‐dose PK profile of rotigaptide. Co‐administration of digoxin with rotigaptide was well tolerated, with no clinically relevant changes in ECGs, blood pressure, pulse, or clinical laboratory data. CONCLUSION There is no pharmacokinetic/pharmacodynamic interaction between rotigaptide and digoxin, and both drugs can be safely coadministered without regard to a dosage adjustment. Clinical Pharmacology & Therapeutics (2005) 79 , P25–P25; doi: 10.1016/j.clpt.2005.12.092