N-(1-carboxy-3-phenylpropyl)phenylalanyl-alpha-asparagine

Summary

N-(1-carboxy-3-phenylpropyl)phenylalanyl-alpha-asparagine is the active diacid form of enalapril (enalaprilat), an ACE inhibitor used in the treatment of hypertension, heart failure, and left ventricular dysfunction. Enalaprilat is the pharmacologically active metabolite generated after de-esterification of the prodrug enalapril maleate in the liver. It is available as an intravenous formulation for situations requiring parenteral ACE inhibition.

Mechanism of Action

Competitive inhibitor of angiotensin-converting enzyme (ACE, kininase II); binds the active site of ACE via its carboxylate and amide groups, preventing cleavage of angiotensin I to angiotensin II and degradation of bradykinin, thereby reducing vasoconstriction and lowering blood pressure.

Routes of Administration

Goals & Uses

• Hypertension managementCardiovascularHigh
• Heart failure treatmentCardiovascularHigh
• Post-myocardial infarction cardioprotectionCardiovascularHigh
• Left ventricular dysfunctionCardiovascularHigh
• Diabetic nephropathy / renoprotectionRenalModerate

Contraindications

• Hereditary or idiopathic angioedemaImmunologic/AllergicHigh
• Pregnancy (2nd and 3rd trimester)ObstetricHigh
• Hypersensitivity to enalapril or any componentAllergicHigh
• Concomitant use with aliskiren in diabetesDrug InteractionHigh
• History of ACE inhibitor-induced angioedemaImmunologic/AllergicHigh

Adverse Effects

• Renal impairment/acute kidney injuryRenalUncommon
• Hypotension (first-dose)CardiovascularCommon
• Elevated serum creatinine/BUNRenalCommon
• HyperkalemiaElectrolyte ImbalanceCommon
• Dry coughRespiratoryCommon
• AngioedemaImmunologicRare

Drug Interactions

• NSAIDs (e.g., ibuprofen, indomethacin)Moderate
• Potassium-sparing diuretics (e.g., spironolactone, amiloride)High
• AliskirenHigh
• Antidiabetic agents (insulin, sulfonylureas)Low
• LithiumModerate

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Pediatric patients (neonates/premature infants)PediatricRelative
• Black patientsEthnicity/PharmacogenomicsRelative
• Severe renal impairment (eGFR <30 mL/min)RenalRelative
• Bilateral renal artery stenosisVascularRelative

Regulatory Status

• European UnionApprovedApproved: Hypertension, Heart failure, Prevention of symptomatic heart failure in patients with asymptomatic LV dysfunctionEnalapril and enalaprilat approved via EMA; multiple national authorizations across EU member states.
• United StatesApprovedApproved: Hypertension (IV for when oral therapy is not practical), Heart failure, Asymptomatic left ventricular dysfunctionEnalaprilat IV (Vasotec IV) approved by FDA. Enalapril maleate oral approved separately. Active diacid form is the IV drug.
• United KingdomApprovedApproved: Hypertension, Heart failure, Prevention of symptomatic heart failureApproved by MHRA; oral enalapril widely available; IV enalaprilat available for hospital use.

Enalaprilat (the active diacid) is FDA-approved as an intravenous formulation (Vasotec IV). Enalapril maleate (prodrug) is widely approved orally across US, EU, and UK. The active diacid form itself is marketed for IV use.

Evidence & Sources

No sources recorded yet.