Article: Losartan

Losartan
Systematic (IUPAC) name
(1-((2'-(2H-tetrazol-5-yl)biphenyl-4-yl)methyl)- 2-butyl-4-chloro-1H-imidazol-5-yl)methanol
Identifiers
CAS number	114798-26-4
ATC code	C09CA01
PubChem	3961
DrugBank	APRD00052
Chemical data
Formula	C22H23ClN6O
Mol. weight	422.91
Pharmacokinetic data
Bioavailability	25–35%
Metabolism	Hepatic (CYP2C9, CYP3A4)
Half life	1.5–2 hours
Excretion	Renal 13–25%, biliary 50–60%
Therapeutic considerations
Pregnancy cat.	D (Au)
Legal status	℞ Prescription only
Routes	Oral

Losartan (rINN) (IPA: [loˈsatən]) is an angiotensin II receptor antagonist drug used mainly to treat high blood pressure (hypertension). Losartan was the first angiotensin II receptor antagonist to be marketed. It is currently marketed by Merck & Co. under the trade name Cozaar.

Clinical use

Main article: Angiotensin II receptor antagonist

As with all angiotensin II receptor antagonists, losartan is indicated for the treatment of hypertension. Losartan may also delay progression of diabetic nephropathy and is also indicated for the reduction of renal disease progression in patients with type 2 diabetes, hypertension and microalbuminuria (>30 mg/24 hours) or proteinuria (>900 mg/24 hours).^[1]

Although angiotensin II receptor antagonists are not usually considered first-line, because of the proven effectivity and lower costs of thiazide diuretics and beta blockers, losartan may be used first-line in patients with increased cardiovascular risk. The LIFE study demonstrated that losartan was significantly superior to atenolol in the primary prevention of adverse cardiovascular events (myocardial infarction or stroke), with a significant reduction in cardiovascular morbidity and mortality for a comparable reduction in blood pressure.^[2]

Combination with diuretic

Losartan is available in a combination formulation with a low dose thiazide diuretic, invariably hydrochlorothiazide, to achieve an additive antihypertensive effect. The losartan/hydrochlorothiazide combination preparation is marketed by Merck under the trade name Hyzaar.

Research

Losartan has been found to downregulate the expression of transforming growth factor beta (TGF-β) types I and II in the kidney of diabetic rats, which may partially account for its nephroprotective effects.^[3] Effects on TGF-β expression may also account for its potential efficacy in Marfan syndrome – losartan has been shown to prevent aortic aneurysm and certain pulmonary complications in a mouse model of the disease.^[4]