LOBENCopy

• DRUGBANK - Losartan
• indication:

  For the treatment of hypertension.

• pharmacology:

• mechanism:

  Losartan and its longer acting active metabolite (E-3174) interfere with the binding of angiotensin II to the angiotensin II AT<sub>1</sub>-receptor by, themselves, binding reversibly to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Neither Losartan or its metabolite inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels.

• toxicity:

  Hypotension and tachycardia; Bradycardia could occur from parasympathetic (vagal) stimulation, LD<sub>50</sub>= 1000 mg/kg (orally in rat)

• absorprion:

  Well absorbed, the systemic bioavailability of losartan is approximately 33%

• halflife:

  The terminal t<sub>1/2</sub> of losartan is 2 hours and that of E-3174 is 6-9 hours.

• roouteelimination:

  After single doses of losartan administered orally, about 4% of the dose is excreted unchanged in the urine and about 6% is excreted in urine as active metabolite. Biliary excretion contributes to the elimination of losartan and its metabolites.

• volumedistribution:

  * 34 L [losartan] * 12 L [active metabolite]

• clearance:

  * 600 mL/min [Healthy volunteers after IV administration] * Renal cl=56 +/- 23 mL/min [Hypertensive adults given 50 mg once daily for 7 days] * Renal cl=53 +/- 33 mL/min [Hypertensive children (6-16 years old) given 0.7 mg/kg once daily for 7 days]