LACK OF EFFECT OF EPROSARTAN ON THE SINGLE-DOSE PHARMACOKINETICS OF ORALLY-ADMINISTERED DIGOXIN IN HEALTHY MALE-VOLUNTEERS

Aims To study the effect of eprosartan, a nonbiphenyl tetrazole angiot ensin II receptor antagonist, on digoxin pharmacokinetics in a randomi zed, open-label, two period, period balanced crossover study in 12 hea lthy men. Methods Each subject received a single 0.6 mg oral dose of d igoxin (Lanoxicaps(R) 0.2 mg/capsule, Glaxo Wellcome) alone or followi ng 3 days of dosing with eprosartan 200 mg orally every 12 h, Each stu dy period was separated by a 14 day washout interval. Serial blood sam ples were obtained for up to 96 h after each digoxin dose for determin ation of digoxin pharmacokinetics. The effect of eprosartan on digoxin pharmacokinetics was assessed through an equivalence-type approach us ing AUC(0, t') as the primary endpoint. Results For AUC(0, t'), the ra tio of digoxin + eprosartan:digoxin alone was 0.99 with a 90% confiden ce interval (CI) of [0.90, 1.09]. For C-max the ratio was 1.00 with a 90% CI of [0.86, 1.17]. t(max) was similar for both regimens. Both reg imens were safe and well tolerated. Conclusions Based on AUC and C-max data, it can be concluded that eprosartan has no effect on the pharma cokinetics of a single oral dose of digoxin.