Investigation of possible pharmacokinetic and pharmacodynamic interactions between epanolol and digoxin

The possibility of a pharmacokinetic and/or pharmacodynamic interaction between epanolol and digoxin has been investigated in 10 healthy male subjects taking digoxin 0.375 mg daily for 14 days. During that period epanolol 200 mg daily or matching placebo was also given, each for 7 days, according to a double-blind, randomized cross-over plan. The plasma digoxin concentration-time profiles after 7 days of concomitant placebo or epanolol were comparable. Trough and peak plasma digoxin levels were similar (placebo: 0.84 and 2.62 ng.ml-1; epanolol: 0.87 and 2.46 ng.ml-1). The renal clearances of digoxin and creatinine were lower during treatment with epanolol, but the differences were not significant (placebo 142.0 and 126.5 ml.min-1; epanolol 105.7 and 109.3 ml.min-1). STI indexes were lower during treatment with digoxin plus epanolol, than after digoxin alone. The difference was significant for QS2I (513 versus 503 ms), PEPI (119 versus 112 ms) and PEP/LVET (0.286 versus 0.304). The observations suggest that in healthy volunteers there is no pharmacokinetic interaction between epanolol and digoxin, and that epanolol does not interfere with the positive inotropic action of digoxin.