Kardiostan Mechanism of Action

Pharmacology: Losartan is a nonpeptide, highly selective angiotensin II subtype I (AT₁) receptor antagonist which relaxes the blood vessels and lowers blood pressure by competing with angiotensin II from binding at the AT₁ receptor. Its active metabolite identified as E3174, binds noncompetitively and irreversibly to AT₁ receptors.
Pharmacokinetics: Losartan is well-absorbed orally from the gastrointestinal tract and has a bioavailability of approximately 33% as a result of the extensive first-pass metabolism. Upon oral administration, 14% of the drug is metabolized in the liver via oxidation by CYP2C9 and CYP3A4 to a more potent active metabolite, E3174. This metabolite is pharmacologically more active than the parent compound, having 20-30 times greater the affinity for AT₁ receptors.
The mean peak concentration (C_max) of losartan is reached 1 hr after administration and 3-4 hrs for its active metabolite. Both losartan and E3174 are >98% protein bound.
The terminal t_½ of the parent drug is about 1.5-2.5 hrs and 3-9 hrs for E3174. Losartan is eliminated via renal (35%) and hepatic (60%) routes as unchanged drug and metabolites.