Lack of effect of eprosartan on the single dose pharmacokinetics of orally administered digoxin in healthy male volunteers

Abstract

Aims To study the effect of eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, on digoxin pharmacokinetics in a randomized, open-label, two period, period balanced crossover study in 12 healthy men. Methods Each subject received a single 0.6 mg oral dose of digoxin (LanoxicapsA 0.2 mg/capsule, Glaxo Wellcome) alone or following 4 days of dosing with eprosartan 200 mg orally every 12 h. Each study period was separated by a 14 day washout interval. Serial blood samples were obtained for up to 96 h after each digoxin dose for determination of digoxin pharmacokinetics. The effect of eprosartan on digoxin pharmacokinetics was assessed through an equivalence-type approach using AUC(0, t∞) as the primary endpoint. Results For AUC(0, t∞), the ratio of digoxin+eprosartan5digoxin alone was 0.99 with a 90% confidence 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 regimens were safe and well tolerated. Conclusions Based on AUC and C max data, it can be concluded that eprosartan has no effect on the pharmacokinetics of a single oral dose of digoxin.

Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension

“…14,15 Since candesartan is not metabolised by the cytochrome P450 system and it has no effect on these enzymes, inhibitors and inducers of the P450 enzymes are not expected to interact with candesartan. 14,15 Eprosartan has no clinically significant effect on the pharmacokinetics of digoxin 157 or the coagulation parameters of warfarin. 158 Similarly, eprosartan has no effect on glucose profile in non-insulindependent diabetic patients stabilized on glyburide.…”

Characterization of a novel impurity in bulk drug eprosartan by ESI/MSn and NMR

“…Two R units were confirmed based on the double proton signals in the 1 16 (s, 2H) in combination with the carbon signal at ı C 30.80 (1C) confirmed the presence of methylene unit. The single peak of aromatic protons at ı H 6.58 and 6.67, which was assigned to the thiophene protons, proved the symmetric connection of 4-4 -2-methyl thiophene with methylene group.…”

“…Eprosartan (4-[2-butyl-5-(2-carboxy-3-thiophen-2-yl-propenyl)-imidazol-1-ylmethyl]-benzoic acid) is a new antihypertensive agent as an angiotensin II receptor antagonist that is highly selective for the typeI (AT1) receptor and that is able to elicit a higher reduction in systolic blood pressure (SBP) than other antihypertensive drugs [1][2][3]. Eprosartan has been authorized to be used in treatment of hyperpiesia, congestive heart failure and renal failure [4], and can be used to treat hypertension disease effectively with good tolerance due to small hazard of serious ill reactions and serious pharmic reactions, and it also has curative effect on secondary preventing cardiovascular and cerebrovascular diseases [5].…”

A Review of Eprosartan Pharmacokinetic and Pharmacodynamic Drug Interaction Studies

“…6 In a randomized, open-label, two-period, period-balanced crossover study, 12 healthy men received a single 0.6-mg oral dose of digoxin (Lanoxicaps 0.2 mg/capsule; Glaxo Wellcome, Research Triangle Park, NC) alone or after 4 days of dosing with eprosartan 200 mg orally every 12 hours. 7 Serial blood samples were obtained for up to 96 hours after each digoxin dose to determine digoxin pharmacokinetics. Eprosartan was considered to have no effect on the area under the curve (AUC) and maximum concentration (C max ) of digoxin if the 90% confidence interval (CI) (digoxin plus eprosartan:digoxin alone) was contained within the range of 0.70-1.43.…”