Source: Health Products Regulatory Authority (ZA) Revision Year: 2024 Publisher: Unichem SA (Pty) Ltd, San Domenico, Ground Floor, Unit G4, 10 Church Street, Durbanville, 7551 Cape Town, Tel: +27 21 531 0436
Category and class: A 7.1.3 Other hypotensives
Pharmacotherapeutic group: Angiotensin II antagonists, plain
ATC code: C09CA01
Losartan is a nonpeptide angiotensin II receptor antagonist with high affinity and selectivity for the AT1 receptor, without binding to or blocking other hormone receptors or ion channels important in cardiovascular regulation. Angiotensin II is a potent vasoconstrictor, a primary active hormone of the renin-angiotensin system, and a major determinant of the pathophysiology of hypertension. Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by inhibiting the binding of angiotensin II to the AT1 receptor.
Losartan is a specific antagonist of the angiotensin II receptor type AT1. Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity during losartan administration. A 2 – 3-fold increase in angiotensin II in plasma comes as a result of increases in plasma renin activity. However, antihypertensive activity and suppression of plasma aldosterone concentration are apparent, indicating effective angiotensin II receptor blockade. After discontinuation of losartan, plasma renin activity and angiotensin levels declined.
Following oral administration, bioavailability is approximately 33%. It undergoes first-pass metabolism to form an active carboxylic acid metabolite, (which has greater pharmacological activity than losartan) and some inactive metabolites. About 14% of an intravenously or orally administered dose is converted to its active metabolite. The mean peak concentrations of losartan and its active metabolite are reached in 1 hour and 3–4 hours, respectively. Both losartan and the carboxylic acid metabolite are greater than, or equal to 99% bound to plasma proteins. The distribution volume of losartan is 34 litres. The terminal half-life of losartan is 2 hours and of its active metabolite is 6–9 hours.
Losartan is excreted in the urine, and in the faeces, as unchanged drug and metabolites. Following oral dosing, about 35% of the dose is excreted in the urine and about 60% in the faeces. Neither losartan nor the active metabolite can be removed by haemodialysis. Plasma concentrations of losartan are not altered in patients with impaired renal function and a creatinine clearance above 10 mL/min. Compared to patients with normal renal function, the AUC for losartan is approximately 2-fold greater in patients on haemodialysis.
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