What is the half-life of enalapril (angiotensin-converting enzyme inhibitor)?

Half-Life of Enalapril

The effective half-life of enalapril's active metabolite, enalaprilat, is 11 hours following multiple doses, though the terminal elimination phase shows a prolonged half-life of approximately 35 hours due to binding to angiotensin-converting enzyme (ACE). 1

Pharmacokinetic Profile

Prodrug Conversion and Absorption

• Enalapril itself is a prodrug that is rapidly absorbed after oral administration, with peak serum concentrations occurring within approximately 1 hour 1, 2
• The prodrug undergoes hepatic esterolysis to convert to enalaprilat, the active diacid metabolite that actually inhibits ACE 1, 3
• Oral bioavailability of enalapril is approximately 60%, though food does not affect absorption 1

Active Metabolite (Enalaprilat) Kinetics

• Peak serum concentrations of enalaprilat occur 3 to 4 hours after oral enalapril administration 1
• The serum concentration profile exhibits a polyphasic decline with a prolonged terminal phase, with enalaprilat detectable up to 96 hours after dosing 2, 4
• This prolonged terminal half-life (>30 hours) represents a small fraction of the administered dose that has been bound to ACE in plasma and does not increase with dose, indicating saturable binding 1, 3

Clinically Relevant Half-Life

• The effective accumulation half-life following multiple doses is 11 hours, which is the clinically relevant parameter for dosing decisions 1, 5
• Steady-state is achieved by the fourth daily dose with no evidence of accumulation 1, 3
• In pediatric patients aged 2 months to ≤16 years, the mean effective half-life for accumulation of enalaprilat at steady state was 14 hours 1

Impact of Renal Function

Normal to Moderate Renal Impairment

• In patients with creatinine clearance >30 mL/min, plasma concentrations are only slightly increased and no dosage adjustment is typically needed 5
• The disposition of enalapril and enalaprilat remains similar to patients with normal renal function until glomerular filtration rate falls to ≤30 mL/min 1

Severe Renal Impairment

• With glomerular filtration rate ≤30 mL/min, peak and trough enalaprilat levels increase significantly, time to peak concentration increases, and time to steady state may be delayed 1
• The effective half-life is prolonged at this level of renal insufficiency, requiring dose reduction to 5 or 2.5 mg per day to avoid considerable accumulation 1, 5
• Enalaprilat is dialyzable at a rate of 62 mL/min 1

Clinical Implications

Dosing Frequency

• The 11-hour effective half-life supports once-daily dosing for most patients, with antihypertensive effects maintained for at least 24 hours at recommended doses 1
• Some patients may experience diminishing effects toward the end of the dosing interval, which may warrant twice-daily dosing 1

Duration of Action

• Following oral administration, onset of antihypertensive activity occurs at 1 hour, with peak blood pressure reduction at 4 to 6 hours 1
• ACE inhibition of more than 50% is maintained for 24 hours following a 20 mg daily dose 5