How long does losartan (angiotensin II receptor antagonist) stay in the bloodstream?

How Long Losartan Stays in the Bloodstream

Losartan has a short half-life of about 2 hours, but its active metabolite E3174 remains in the bloodstream for 6-9 hours, providing a 24-hour therapeutic effect with once-daily dosing. 1, 2

Pharmacokinetics of Losartan

• Losartan is rapidly absorbed after oral administration, reaching maximum plasma concentrations within 1-2 hours post-administration 2
• The systemic bioavailability of losartan is approximately 33% due to first-pass metabolism 1
• Losartan undergoes substantial metabolism in the liver, with about 14% converted to its active metabolite E3174 1, 2
• The active metabolite E3174 is 10-40 times more potent than losartan itself and is responsible for most of the angiotensin II receptor antagonism 1, 2

Elimination Parameters

• The terminal half-life of losartan is approximately 2 hours 1, 2
• The active metabolite E3174 has a longer half-life of 6-9 hours 1, 2
• Total plasma clearance of losartan is about 600 mL/min, with renal clearance accounting for approximately 75 mL/min 1
• Total plasma clearance of the active metabolite is about 50 mL/min, with renal clearance of about 25 mL/min 1

Duration of Action

• Despite losartan's short half-life, its therapeutic effect persists for 24 hours due to the longer-lasting active metabolite 2, 3
• A dose of 100 mg inhibits the pressor effect of angiotensin II by about 85% at peak, with 25-40% inhibition persisting for 24 hours 1
• The pharmacokinetics of losartan and its active metabolite are linear and do not change over time with repeated administration 1, 2

Excretion Pathways

• After single oral doses of losartan, approximately 4% is excreted unchanged in urine and about 6% is excreted in urine as the active metabolite 1
• Biliary excretion contributes significantly to the elimination of losartan and its metabolites 1
• Following oral administration of radiolabeled losartan, about 35% of radioactivity is recovered in urine and about 60% in feces 1

Clinical Implications

• The once-daily dosing regimen of losartan is supported by its pharmacokinetic profile, particularly the long half-life of its active metabolite 2, 4
• There is no apparent rebound effect after abrupt withdrawal of losartan 1
• No dosage adjustment is necessary for mild hepatic impairment or various degrees of renal insufficiency 2
• Neither losartan nor its active metabolite accumulates in plasma upon repeated once-daily dosing 1

Special Considerations

• Food slows the absorption of losartan and decreases its maximum concentration but has only minor effects on the overall exposure (AUC) of losartan or its metabolite (approximately 10% decrease) 1
• Age, sex, and race do not significantly affect the pharmacokinetics of losartan, requiring no dosage adjustments based on these factors 2
• Losartan or its active metabolite is not removed during hemodialysis 2

The pharmacokinetic profile of losartan supports its clinical efficacy throughout a 24-hour period despite its relatively short half-life, making it suitable for once-daily administration in the management of hypertension and other cardiovascular conditions 2, 5, 6.