Duration of Action of Losartan
Losartan provides 24-hour blood pressure control with once-daily dosing, though its antihypertensive effect diminishes toward the end of the dosing interval, with 25-40% of peak inhibition persisting at 24 hours. 1
Pharmacokinetic Profile
The terminal half-life of losartan itself is approximately 2 hours, while its active metabolite (E-3174) has a half-life of 6-9 hours. 1 This active metabolite is responsible for most of the therapeutic effect and is 10-40 times more potent than the parent compound. 1, 2
- Losartan reaches peak plasma concentrations in 1 hour after oral administration 1
- The active metabolite E-3174 reaches peak concentrations in 3-4 hours 1
- Only about 14% of an oral losartan dose is converted to the active metabolite, but the metabolite's area under the curve (AUC) is approximately 4 times greater than losartan itself 1
Duration of Antihypertensive Effect
A 100 mg dose of losartan inhibits the pressor effect of angiotensin II by approximately 85% at peak, with 25-40% inhibition persisting for 24 hours. 1 This pharmacodynamic profile supports once-daily dosing for most patients.
- The antihypertensive effect is substantially present within one week, though maximal effect may take 3-6 weeks in some patients 1
- In long-term studies, the effect of losartan was maintained for up to one year 1
- There is no apparent rebound effect after abrupt withdrawal 1
Clinical Dosing Implications
For optimal 24-hour blood pressure control, the standard dose is 50-100 mg once daily, though some patients may benefit from twice-daily dosing at higher total daily doses. 3
- The American College of Cardiology/American Heart Association guidelines list losartan's usual dose range as 50-100 mg/day with a daily frequency of "1 or 2" 3
- For heart failure with reduced ejection fraction, the target dose is 100 mg once daily 4, 3
- Higher doses (150 mg daily) may require twice-daily administration (75 mg twice daily) for more consistent 24-hour coverage 3
Trough-to-Peak Ratio
Studies using ambulatory blood pressure monitoring demonstrate that losartan maintains adequate antihypertensive effect throughout the 24-hour dosing interval. 5 A study with extended-release losartan formulation showed a trough-to-peak ratio of 0.91 for systolic blood pressure and 1.14 for diastolic blood pressure, with significant blood pressure reduction maintained during the last 4 hours before the next dose. 5
Common Pitfalls to Avoid
- Do not assume losartan provides identical blood pressure control throughout the entire 24-hour period - the effect is strongest in the first 12 hours and diminishes toward the end of the dosing interval 1
- Avoid underdosing - clinical trials support 100 mg daily as the target dose for optimal cardiovascular outcomes in heart failure, yet less than 25% of patients are titrated to target doses in clinical practice 3
- Monitor blood pressure at trough (just before the next dose) to ensure adequate 24-hour control, as this is when the drug effect is weakest 5