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| Clinical data | |
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| AHFS/Drugs.com | Monograph |
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| ECHA InfoCard | 100.071.306 |
| Chemical and physical data | |
| Formula | C18H24N2O5 |
| Molar mass | 348.399 g·mol−1 |
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Enalaprilat is theactive metabolite ofenalapril. It is the first dicarboxylate-containingACE inhibitor and was developed partly to overcome these limitations ofcaptopril. Thethiolfunctional group of captopril was replaced with acarboxylic 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 itsionisation characteristics do not allow for sufficient GI absorption. Thus, enalaprilat was only suitable forintravenous administration. This was overcome by the monoesterification of enalaprilat withethanol to produceenalapril.
As aprodrug, enalapril is hydrolyzedin vivo to the active form enalaprilat by variousesterases. 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.[2][3]
