Pharmacokinetics of intravenously and orally administered eprosartan in healthy males: Absolute bioavailability and effect of food

Abstract

Eighteen healthy males received a single 300 mg oral dose of eprosartan as the commercial wet granulation formulation under fasting conditions and following a high-fat breakfast and a single 20 mg intravenous (i.v.) dose. The pharmacokinetics of i.v. eprosartan (mean ± S.D.) were characterized by a low systemic plasma clearance (131.8 ± 36.2 mL min-1) and a small steady-state volume of distribution (12.6 ± 2.6 L). Oral bioavailability averaged 13.1%, due to incomplete absorption. In vitro dynamic flow cell dissolution data showed that pH-dependent aqueous solubility of eprosartan is one factor which limits absorption. Eprosartan terminal half-life was shorter. after i.v. (approximately 2 h) versus oral (approximately 5-7 h) administration, which may be due to detection of an additional elimination phase or absorption rate-limited elimination following oral administration. Oral administration of eprosartan following a high-fat meal compared with fasting conditions resulted in a similar extent of absorption (based on AUC), but a decreased absorption rate. C(max) was approximately 25% lower, and a median delay of 1.25 h in time to C(max) was observed when eprosartan was administered with food. These minor changes in exposure are unlikely to be of clinical consequence; therefore, eprosartan may be administered without regard to meal times.