When does Losartan (losartan) reach its peak effect in most people?

Peak Effect of Losartan in Most People

Losartan reaches its peak plasma concentration within 1 hour after oral administration, but its maximum therapeutic effect occurs 3-4 hours after administration when its active metabolite E3174 reaches peak levels. 1

Pharmacokinetic Profile of Losartan

Losartan undergoes significant first-pass metabolism after oral administration. The drug has a dual mechanism of action:

• Parent compound (Losartan):

  • Rapidly absorbed after oral administration
  • Peak plasma concentration reached in 1 hour 1
  • Terminal half-life of approximately 2 hours 1
  • Systemic bioavailability of approximately 33% 1

• Active metabolite (E3174):

  • Formed through metabolism by cytochrome P450 enzymes
  • Peak plasma concentration reached in 3-4 hours 1
  • Terminal half-life of 6-9 hours 1
  • 10-40 times more potent than parent compound 2
  • Responsible for most of the angiotensin II receptor antagonism 1

Clinical Significance of Dual Action

The therapeutic effect of losartan depends on both the parent compound and its active metabolite:

• Initial blood pressure lowering begins with losartan (1 hour)
• Maximum therapeutic effect occurs when E3174 reaches peak levels (3-4 hours) 1, 3
• The longer half-life of E3174 (6-9 hours) allows for once-daily dosing despite the shorter half-life of the parent compound 1

Factors Affecting Peak Effect

Several factors can influence when losartan reaches its peak effect:

• Food intake: A meal slows absorption of losartan and decreases its maximum concentration (Cmax) but has only minor effects on the area under the curve (AUC) of losartan or its metabolite (approximately 10% decrease) 1
• Age and gender: No clinically significant effects on pharmacokinetics, so no dosage adjustment is necessary 1
• Renal function: No significant change in peak effect timing, though plasma concentrations may be increased in patients with renal insufficiency 1
• Hepatic function: Patients with mild to moderate hepatic impairment may have doubled oral bioavailability and require lower starting doses 1

Clinical Implications

Understanding the peak effect timing of losartan has important clinical implications:

• Blood pressure monitoring should ideally occur around 3-4 hours post-dose to capture maximum effect
• For patients with inadequate 24-hour blood pressure control on once-daily dosing, splitting the dose into twice-daily dosing may be considered 4
• The full therapeutic effect of losartan may not be apparent until steady-state concentrations are reached after 2-3 days of consistent dosing 2

Losartan's dual mechanism with both the parent compound and active metabolite provides a more sustained antihypertensive effect throughout the 24-hour dosing interval compared to what would be expected from the half-life of losartan alone.