What is the half-life of perindopril (Angiotensin-Converting Enzyme (ACE) inhibitor)?

Half-Life of Perindopril

The half-life of perindopril is approximately 0.8 to 1.0 hours, while its active metabolite perindoprilat has a terminal elimination half-life of 30 to 120 hours. 1

Pharmacokinetic Properties of Perindopril

Perindopril is a prodrug that requires de-esterification to perindoprilat, its active metabolite, to exert its angiotensin-converting enzyme (ACE) inhibitory effects. The pharmacokinetic profile includes:

• Absorption: Rapid absorption with peak plasma concentrations occurring at approximately 1 hour 1
• Bioavailability: Absolute oral bioavailability is about 75% 1
• Metabolism: After absorption, approximately 30-50% of systemically available perindopril is hydrolyzed to perindoprilat 1
• Distribution: Perindoprilat peak plasma concentrations are attained 3-7 hours after perindopril administration 1

Half-Life Characteristics

Perindopril exhibits multiexponential pharmacokinetics following oral administration:

• Perindopril (prodrug): Mean half-life of approximately 0.8 to 1.0 hours for most of its elimination 1
• Perindoprilat (active metabolite):
  • Initial phase: Mean half-life of 3-10 hours for the majority of elimination 1
  • Terminal phase: Prolonged terminal elimination half-life of 30-120 hours due to slow dissociation from plasma/tissue ACE binding sites 1

Clinical Implications of Perindopril's Half-Life

The pharmacokinetic profile of perindopril has several important clinical implications:

• Once-daily dosing: Despite the short half-life of the parent compound, the prolonged terminal half-life of perindoprilat allows for once-daily dosing 2
• Steady state: Perindoprilat accumulates about 1.5-2.0 fold and attains steady-state plasma levels in 3-6 days 1
• Missed doses: Studies show that most of the antihypertensive effect remains for 24-48 hours after dosing, providing protection to patients who miss a dose 3

Special Populations

The half-life and pharmacokinetics of perindopril are affected in certain populations:

• Elderly patients: Plasma concentrations of both perindopril and perindoprilat are approximately twice those observed in younger patients 1
• Renal impairment: The half-life of perindoprilat increases significantly with decreasing renal function, varying from 5.0 hours in subjects with normal renal function to 27.4 hours in patients with severe renal failure 4
• Heart failure: Perindoprilat clearance is reduced in congestive heart failure patients, resulting in a 40% higher dose interval AUC 1

Clinical Considerations

• Perindopril and perindoprilat are dialyzable 4
• Dosage adjustment is necessary in patients with renal impairment due to the significant impact on perindoprilat elimination 4
• The prolonged terminal elimination half-life contributes to the drug's 24-hour efficacy with once-daily dosing 3

The unique pharmacokinetic profile of perindopril, particularly the extended terminal half-life of its active metabolite perindoprilat, contributes to its clinical utility as an effective once-daily ACE inhibitor for treating hypertension and other cardiovascular disorders.