The effect of renal function on enalapril kinetics

Area of Science:

• Pharmacology
• Nephrology
• Drug Metabolism

Background:

• Enalapril maleate is an orally active prodrug converted to enalaprilat, the active angiotensin-converting enzyme (ACE) inhibitor.
• Renal function significantly impacts drug pharmacokinetics, necessitating studies on drug behavior in patients with kidney disease.

Purpose of the Study:

• To evaluate the serum profiles and urinary excretion of oral enalapril maleate in patients with varying degrees of renal impairment.
• To compare the pharmacokinetic behavior of enalapril maleate in patients with renal disease versus healthy subjects.

Main Methods:

• Oral enalapril maleate (10 mg) was administered to three groups: severe renal disease (creatinine clearance < 3 ml/min, n=10), moderate renal disease (10-79 ml/min, n=9), and healthy controls (>80 ml/min, n=10).
• Blood and urine samples were collected over 48 hours post-administration.
• Enalaprilat was confirmed to be dialyzable.

Main Results:

• Patients with impaired renal function exhibited elevated serum and plasma concentrations of enalapril maleate.
• Reduced excretion rates and urinary recovery of both enalapril maleate and enalaprilat were observed in patients with renal disease.
• Data suggest increased metabolism to enalaprilat or enhanced nonrenal elimination of unchanged enalapril maleate in renal impairment.

Conclusions:

• Renal impairment significantly alters the pharmacokinetics of enalapril maleate, leading to higher systemic exposure.
• The active metabolite, enalaprilat, is effectively removed by dialysis, which is a crucial consideration for patients undergoing this procedure.
• Dosage adjustments or careful monitoring may be necessary for patients with compromised renal function receiving enalapril maleate.