Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: Ranbaxy Pharmaceuticals (Pty) Ltd, 14 Lautre Road, Stormill, Ext. 1, Roodepoort, 1724, South Africa
Category and class: A 7.1.3 Vascular medicines – Other hypotensives
Pharmacotherapeutic group: Angiotensin Converting Enzyme (ACE) inhibitor
ATC Code: C09AA02
Following oral administration and absorption, enalapril is hydrolysed to enalaprilat which is a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor. Enalapril is a derivative of two amino acids; L-alanine and L-proline. ACE is a peptidyl dipeptidase which catalyses the conversion of angiotensin I to the pressor substance angiotensin II. This results in reduced plasma renin activity and decreased aldosterone secretion. The blood pressure lowering effect of enalapril is primarily through suppression of the renin- angiotensin- aldosterone system.
Oral enalapril is absorbed, with peak serum concentrations of enalapril occurring within one hour. Based on urinary recovery, the extent of absorption of enalapril from oral enalapril tablet is approximately 60%. The absorption of oral enalapril is not influenced by the presence of food in the gastrointestinal tract.
Following absorption, oral enalapril is rapidly and extensively hydrolysed to enalaprilat, an angiotensin converting enzyme inhibitor. Peak serum concentrations of enalaprilat occur about 4 hours after an oral dose of enalapril tablet. The effective half-life of enalaprilat following multiple doses of oral enalapril is 11 hours. In subjects with normal renal function, steady-state serum concentrations of enalaprilat were reached after 4 days of treatment.
Over the range of concentrations which are therapeutically relevant, enalaprilat binding to human plasma proteins does not exceed 60%.
Except for conversion to enalaprilat, there is no evidence for significant metabolism of enalapril.
Excretion of enalaprilat is primarily renal. The principal components in urine are enalaprilat, accounting for about 40% of the dose, and intact enalapril (about 20%).
The exposure of enalapril and enalaprilat is increased in patients with renal insufficiency. In patients with mild to moderate renal insufficiency (creatinine clearance 40-60 ml/min) steady state AUC was approximately two-fold higher than in patients with normal renal function after administration of 5 mg once daily. In severe renal impairment (creatinine clearance ≤30 ml/min), AUC was increased approximately 8-fold. The effective half-life of enalaprilat following multiple doses of enalapril maleate is prolonged at this level of renal insufficiency and time to steady state is delayed (see Section 4.2, Dosage in Renal Insufficiency). Enalaprilat may be removed from the general circulation by haemodialysis.
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