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an ACE inhibitor (trade name Vasotec) that blocks the formation of angiotensin in the kidney and so results in vasodilation; administered after heart attacks (同)Vasotec

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/05 23:59:11」(JST)

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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 sulfhydryl-moiety was replaced by a carboxylate-moiety, but additional modifications were required in its structure-based design to achieve a similar potency to captopril.

Enalaprilat, however, had a problem of its own. The consequence of the structural modifications was that it proved to have unfavourable ionisation characteristics to allow sufficient potency for oral administration (in tablets). Thus, enalaprilat was only suitable for intravenous administration. This was overcome by the esterification of enalaprilat with ethanol to produce enalapril.

As a prodrug, enalapril is metabolized 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

^ D. J. Tocco et al. (1982). "The physiological disposition and metabolism of enalapril maleate in laboratory animals". Drug Metab Dispos. 10 (15): 15–19.
^ A. C. Simon et al. (1988). "Acute Hemodynamic Effects in Essential Hypertension". Clin. Pharm. Ther. 43 (49).

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English Journal

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome.

Raghunathan V1, Sethi SK2, Dragon-Durey MA3, Dhaliwal M1, Raina R4, Jha P2, Bansal SB2, Kher V2.
Indian journal of nephrology.Indian J Nephrol.2017 Mar-Apr;27(2):136-140. doi: 10.4103/0971-4065.181462.
PMID 28356668

99mTc-MAG3: Image Wisely.

Taylor AT1, Folks RD1, Rahman AK1, Polsani A1, Dubovsky EV1, Halkar R1, Manatunga A1.
Radiology.Radiology.2017 Feb 17:152311. doi: 10.1148/radiol.2017152311. [Epub ahead of print]
PMID 28212051

LC-MS/MS assay for quantitation of enalapril and enalaprilat in plasma for bioequivalence study in Indian subjects.

Halder D1, Dan S1, Pal MM2, Biswas E1, Chatterjee N2, Sarkar P1, Halder UC3, Pal TK1.
Future science OA.Future Sci OA.2017 Feb 2;3(1):FSO165. doi: 10.4155/fsoa-2016-0071. eCollection 2017.
PMID 28344828

Japanese Journal

銅及び亜鉛キレート形成によるangiotensin-converting enzyme（ACE）阻害剤エナラプリラトの脂溶性増加

藤岡晴人,稗田雄三,倉本康弘 [他],小西華那世,木下(菊田) 恵美子,木下英司,小池透
薬学雑誌. 乙号 133(10), 1135-1141, 2013
… Enalaprilat (H2L), which is the active metabolite of the pro-drug enalapril, is an angiotensin-converting enzyme inhibitor. … For a better understanding of this phenomenon, we investigated the solution species of enalaprilat in the presence of copper(II) or zinc(II) ions by pH titration analysis with I=0.10 M (NaCl) at 25℃. …
NAID 130003361996

Simultaneous determination of enalapril and enalaprilat in human plasma by liquid chromatography-tandem mass spectrometry

GU Qi,CHEN Xiaoyan,ZHONG Dafang,WANG Yingwu
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 813(1), 337-342, 2004-11-25
NAID 10016540865

Protective Effects of Quinaprilat and Trandolaprilat, Active Metabolites of Quinapril and Trandolapril, on Hemolysis Induced by Lysophosphatidylcholine in Human Erythrocytes

, , [他], , ,
Biological & pharmaceutical bulletin 26(5), 712-716, 2003-05-01
… We examined the effects of the angiotensin converting enzyme (ACE) inhibitors captopril, enalaprilat, quinapril, and trandolapril, and their active metabolites quinaprilat and trandolaprilat, on hemolysis induced by lysophosphatidylcholine (LPC) in human erythrocytes. …
NAID 110003608503

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★リンクテーブル★

リンク元	「エナラプリラト」「エナラプリラート」

「エナラプリラト」

Systematic (IUPAC) name
	(2S)-1-[(2S)-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}propanoyl]pyrrolidine-2-carboxylic acid
Clinical data
AHFS/Drugs.com	monograph
Licence data	US FDA:link
Identifiers
CAS Registry Number	76420-72-9
IUPHAR/BPS	6332
ChemSpider	4575429
UNII	GV0O7ES0R3
ChEBI	CHEBI:4786
ChEMBL	CHEMBL577
Chemical data
Formula	C18H24N2O5
Molecular mass	348.4 g/mol
	SMILES C[C@H](N[C@@H](CCc1ccccc1)C(=O)O)C(=O)N2CCC[C@H]2C(=O)O ;
	InChI InChI=1S/C18H24N2O5/c1-12(16(21)20-11-5-8-15(20)18(24)25)19-14(17(22)23)10-9-13-6-3-2-4-7-13/h2-4,6-7,12,14-15,19H,5,8-11H2,1H3,(H,22,23)(H,24,25)/t12-,14-,15-/m0/s1 ; Key:LZFZMUMEGBBDTC-QEJZJMRPSA-N ;