Chemistry:Enalaprilat
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| AHFS/Drugs.com | Monograph |
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| Formula | C18H24N2O5 |
| Molar mass | 348.399 g·mol−1 |
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Enalaprilat is the active metabolite of enalapril. It is the first dicarboxylate-containing ACE inhibitor and was developed partly to overcome these limitations of captopril. The thiol functional group of captopril was replaced with a carboxylic acid group, but additional modifications were required to achieve a potency similar to captopril.
Enalaprilat, however, had a problem of its own. The consequence of the structural modifications was that its ionisation characteristics do not allow for sufficient GI absorption. Thus, enalaprilat was only suitable for intravenous administration. This was overcome by the monoesterification of enalaprilat with ethanol to produce enalapril.
As a prodrug, enalapril is hydrolyzed in vivo to the active form enalaprilat by various esterases. Peak plasma enalaprilat concentrations occur 2 to 4 hours after oral enalapril administration. Elimination thereafter is biphasic, with an initial phase which reflects renal filtration (elimination half-life 2 to 6 hours) and a subsequent prolonged phase (elimination half-life 36 hours), the latter representing equilibration of drug from tissue distribution sites.
The prolonged phase does not contribute to drug accumulation on repeated administration but is thought to be of pharmacological significance in mediating drug effects. Renal impairment [particularly creatinine clearance <20 mL/min (<1.2 L/h)] results in significant accumulation of enalaprilat and necessitates dosage reduction. Accumulation is probably the cause of reduced elimination in healthy elderly individuals and in patients with concomitant diabetes, hypertension and heart failure.[1][2]
References
- ↑ "The physiological disposition and metabolism of enalapril maleate in laboratory animals". Drug Metabolism and Disposition 10 (1): 15–9. 1982. PMID 6124377.
- ↑ "Brachial artery hemodynamic response to acute converting enzyme inhibition by enalaprilat in essential hypertension". Clinical Pharmacology and Therapeutics 43 (1): 49–54. January 1988. doi:10.1038/clpt.1988.10. PMID 2826067.
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