Pharmacokinetics of intravenously and orally administered eprosartan in healthy males: absolute bioavailability and effect of food.
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.
Tenero
D
D
Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, King of Prussia, PA, USA.
Martin
D
D
Ilson
B
B
Jushchyshyn
J
J
Boike
S
S
Lundberg
D
D
Zariffa
N
N
Boyle
D
D
Jorkasky
D
D
D000179:Acrylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D013876:Thiophenes
D000179:Acrylates; D000959:Antihypertensive Agents; D004041:Dietary Fats; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan