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Pharmacology: Pharmacodynamics: Losartan is an angiotensin-II-receptor antagonist with antihypertensive activity mainly due to selective blockade of AT receptors and the consequent reduced press or effect of angiotensin II.
Pharmacokinetics: Losartan is readily absorbed from the gastrointestinal tract following oral administration, with an oral bioavailability of about 33%. It undergoes first-pass metabolism to form an active carboxylic acid metabolite E-3174 (EXP-2174), which has greater pharmacological activity than losartan, and some inactive metabolites. Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of losartan and E-3174 occur about 1 hour and 3 to 4 hours, respectively, after an oral dose. Both losartan and E-3174 are more than 98% bound to plasma proteins. Losartan is excreted in the urine and in the faeces via bile, as unchanged drug and metabolites. Following oral dosing, 35% of the dose is excreted in the urine and about 60% in the faeces. The terminal elimination half-lives of losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.
