Pharmacology: Pharmacokinetics: Losartan is readily absorbed from the gastrointestinal tract after oral doses, but undergoes substantial first-pass metabolism resulting in a systemic bioavailability of about 33%. It is metabolized to an active carboxylic acid metabolite E-3174 (EXP-3174), which has greater pharmacological activity than losartan; some inactive metabolites are also formed. 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. About 4% of an oral dose is excreted unchanged in urine and about 6% is excreted in urine as the active metabolite. The terminal elimination half-lives of losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.
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