Neosartan Mechanism of Action

Pharmacology: Pharmacodynamics: Losartan inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. A dose of 100 mg inhibits the pressor effect by about 85% at peak with 25-40% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a doubling to tripling in plasma renin activity and consequent rise in angiotensin II plasma concentration in hypertensive patients. Losartan does not affect the response to bradykinin, whereas ACE inhibitors increase the response to bradykinin. Aldosterone plasma concentrations fall following losartan administration. In spite of the effect of losartan on aldosterone secretion, very little effect on serum potassium was observed.
The effect of losartan is substantially present within one week but in some studies the maximal effect occurred in 3-6 weeks. In long-term follow-up studies (without placebo control) the effect of losartan appeared to be maintained for up to a year. There is no apparent rebound effect after abrupt withdrawal of losartan. There was essentially no change in average heart rate in losartan-treated patients in controlled trials.
Pharmacokinetics: Losartan potassium is an angiotensin II receptor antagonist with antihypertensive activity due mainly to selective blockage of AT₁ receptors and the consequent reduced pressure effect on angiotensin II.
Losartan potassium 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-3174), which has greater pharmacological activity than Losartan and some inactive metabolites. Metabolism is primarily by cytochrome P450 isoenzyme 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 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 of Losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours respectively.