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Irbesartan exhibits linear pharmacokinetics over the therapeutic dose range. The terminal elimination half-life of irbesartan averaged 11-15 hours. Steady-state concentrations are achieved within 3 days. Limited accumulation of irbesartan (<20%) is observed in plasma upon repeated once-daily dosing. Metabolism and Elimination Text Continues Below
Irbesartan is metabolized via glucuronide conjugation and oxidation. Following oral or intravenous administration of 14C-labeled irbesartan, more than 80% of the circulating plasma radioactivity is attributable to unchanged irbesartan. The primary circulating metabolite is the inactive irbesartan glucuronide conjugate (approximately 6%). The remaining oxidative metabolites do not add appreciably to irbesartan's pharmacologic activity. Irbesartan and its metabolites are excreted by both biliary and renal routes. Following either oral or intravenous administration of 14C-labeled irbesartan, about 20% of radioactivity is recovered in the urine and the remainder in the feces, as irbesartan or irbesartan glucuronide. In vitro studies of irbesartan oxidation by cytochrome P450 isoenzymes indicated irbesartan was oxidized primarily by 2C9; metabolism by 3A4 was negligible. Irbesartan was neither metabolized by, nor did it substantially induce or inhibit, isoenzymes commonly associated with drug metabolism (1A1, 1A2, 2A6, 2B6, 2D6, 2E1). There was no induction or inhibition of 3A4. Distribution Irbesartan is 90% bound to serum proteins (primarily albumin and 1 -acid glycoprotein) with negligible binding to cellular components of blood. The average volume of distribution is 53-93 liters. Total plasma and renal clearances are in the range of 157-176 and 3.0-3.5 mL/min, respectively. With repetitive dosing, irbesartan accumulates to no clinically relevant extent. Studies in animals indicate that radiolabeled irbesartan weakly crosses the blood brain barrier and placenta. Irbesartan is excreted in the milk of lactating rats. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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