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

1998; Wiley; Volume: 19; Issue: 6 Linguagem: Inglês

10.1002/(sici)1099-081x(199809)19

1099-081X

David M. Tenero, David E. Martin, Bernard E. Ilson, John Jushchyshyn, Steve Boike, David Lundberg, Névine Zariffa, Duane Boyle, Diane Jorkasky,

Cardiac pacing and defibrillation studies

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. Cmax was approximately 25% lower, and a median delay of 1.25 h in time to Cmax 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. © 1998 John Wiley & Sons, Ltd.