Pharmacokinetics of eprosartan in healthy subjects, patients with hypertension, and special populations.
After oral administration of eprosartan to healthy volunteers, bioavailability is approximately 13%, with peak plasma concentrations occurring 1-2 hours after an oral dose in the fasted state. Food slows the rate of absorption and changes the overall extent by less than 25%, which is unlikely to be of clinical consequence. Plasma concentrations increase in a slightly less than dose-proportional manner from 100-800 mg. There is no evidence of significant accumulation of eprosartan with long-term therapy. The drug's terminal elimination half-life is typically 5-9 hours after oral administration. The agent is highly protein bound (approximately 98%), with low plasma clearance (approximately 130 ml/minute) and small volume of distribution (approximately 13 L). It is primarily unmetabolized by the liver, with less than 2% of an oral dose recovered in the urine as a glucuronide. Biliary (primary) and renal excretion contribute to its elimination. No dosage adjustment is required in patients with mild to moderate renal impairment. Although an increase in systemic exposure to eprosartan was observed in the elderly, in patients with hepatic impairment, and in those with severe renal disease, this finding is unlikely to be of clinical consequence, based on the drug's excellent safety and tolerability profile (doses up to 1200 mg) in phase III clinical trials in hypertensive patients. Eprosartan can be safely administered to these special populations without an initial dosage adjustment, with subsequent dosing individualized based on tolerability and response.
Bottorff
M B
MB
College of Pharmacy, University of Cincinnati, Ohio 45267-0004, USA.
Tenero
D M
DM
D000042:Absorption; D000179:Acrylates / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000367:Age Factors; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000633:toxicity; D001682:Biological Availability; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012737:Sex Factors; D013876:Thiophenes
D000179:Acrylates; D000959:Antihypertensive Agents; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan