Besartan Mechanism of Action

Pharmacology: Pharmacodynamics: Losartan potassium represents the 1st of a new class of antihypertensives, is a specific angiotensin-II receptor (type AT₁) antagonist. Angiotensin II is a potent vasoconstrictor and the primary active hormone of the renin-angiotensin-aldosterone system, playing a major part in the pathophysiology of
hypertension. The cardiovascular homeostatic effects of angiotensin II are elicited through the AT₁ receptor. Losartan is a potent, synthetic orally active compound, which binds selectively to the AT₁ receptor. In vitro and In vivo, both losartan and its pharmacologically active metabolite, E-3174 block all physiologically relevant actions of angiotensin II including vasoconstriction, sodium and water retention and sympathetic stimulation. This leads to reduction in the blood pressure. Losartan does not have agonist effects and does not bind or block other hormone receptors or ion channels important in cardiovascular regulation.
Pharmacokinetics: Following oral administration, losartan potassium is well absorbed and undergoes substantial first-pass metabolism; the systemic bioavailability is approximately 33%. It undergoes first-pass metabolism to form an active carboxylic acid metabolite E-3174 (EXP-317), which has greater pharmacological activity than losartan and E-3174 occur about 1 hr and 3-4 hrs, respectively, after an oral dose. Both losartan and E-3174 are >98% bound to plasma proteins. Losartan is excreted in the urine, and in the feces via bile, as unchanged drug and metabolites. Following oral dosing about 35% of the dose is excreted in the urine and about 60% in the feces. The terminal elimination half-lives (t_½) of losartan and E-3174 are about 1.5-2.5 hrs and 3-9 hrs, respectively.