EFFECT OF TENIDAP SODIUM ON DIGOXIN PHARMACOKINETICS IN HEALTHY-YOUNGMEN

1 The effects of tenidap sodium and placebo on digoxin pharmacokinetic s were compared in 14 healthy young men, in a double-blind, parallel-g roup study lasting for 24 days. 2 Subjects were administered digoxin a lone for the first 10 days and digoxin plus tenidap 120 mg day(-1) or placebo for the remaining 14 days. 3 Changes in the means between day 10 (digoxin monotherapy) and day 24 (combined therapy) for renal clear ance, area under the plasma concentration-time curve during the dosing interval, and the minimum and maximum plasma digoxin concentrations d id not differ significantly between the tenidap and placebo groups. Th ere was a small but statistically significant increase (0.5 h) in the time taken to reach maximum plasma digoxin concentration following 14 days' continuous tenidap co-administration compared with placebo, but this was not considered to be clinically meaningful. 4 Co-administrati on of tenidap and digoxin was well tolerated. No subject withdrew from the study during combination treatment. Treatment-related adverse eve nts were of mild to moderate severity and were reported by four subjec ts on digoxin monotherapy, four on tenidap and digoxin, and by two on digoxin and placebo. Those reported by the tenidap group predominantly affected the gastrointestinal system and were mild in severity. There were no reports of laboratory test abnormalities or cardiovascular ab normalities related to combined digoxin and tenidap administration. 5 The results of this study indicate that, in healthy young men, co-admi nistration of tenidap with digoxin does not have any apparent clinical ly significant effects on the pharmacokinetic profile of digoxin, and the treatment is well tolerated.