Introduction
Perindopril erbumine is an angiotensioncon vertingenzyme (ACE) inhibitor without sulfhydryl group. It is a chiral drug with good clinical efficacy, high safety and small side effects among the international antihypertensive drugs of angiotensin converting enzyme inhibitor (ACEIs). Perindopril has a good clinical effect on improving vascular structure and function of patients with hypertension. In the route for the synthesis of perindopril by the active ester method, (2S, 3aS, 7aS)-octahydroindo le-2-carboxylic acid and N-[(S)-1-carbethoxy-1-buty l]-(S)-alanine are used as raw materials.
Pharmacologic action
Perindopril erbumine is an angiotensin converting enzyme inhibitor (ACEI). Angiotensin-converting enzyme can transform inactive angiotensin I to active angiotensin II. Angiotensin can cause obvious vasoconstriction and stimulate the secretion of aldosterone in the adrenal cortex. Perindopril erbumine can lead to the following conditions: (1) aldosterone secretion; (2) increased renin activity due to the lack of aldosterone secondary feedback; (3) decreased peripheral arterial resistance, and priority of the muscle and renal blood flow without sodium and fluid retention or reflex tachycardia after long-term use. Like all invertase inhibitors, Perindopril erbumine inhibits strong peptide vasodilators - bradykinin degrading into inactive peptides. Perindopril erbumine can lower blood pressure in patients with low renin levels or normal renin levels.
Function
Perindopril is an effective antihypertensive, well-tolerated angiotensin-converting enzyme inhibitor with high affinity for angiotensin converting enzyme. It has anti-ischemic, anti-atherosclerotic, and vascular protection characteristics, so it can be used in the treatment of hypertension and congestive heart failure. It can reduce the mortality of hypertensive patients and the occurrence of cardiovascular events.
Pharmacokinetics and metabolism
Perindopril erbumine is quickly absorbed and 65-70% of perindopril erbumine is hydrolyzed into perindoprilat. Perindoprilat is a specific angiotensin-converting enzyme inhibitor. The amount of perindoprilat is influenced by the diet. Plasma protein binding rate is less than 30%, and is concentration dependent. After taking perindopril erbumine once a day, the average steady state concentration can last for four days, and the effective cumulative half-life is about 24 hours. In cirrhotic patients, the kinetics of perindopril erbumine chenges: the liver clearance of maternal molecules is halved. However, the production of perindoprilat does not decrease, and there is no need to adjust the dosage. ACE inhibitors can pass through the placenta.
References:
Yang, X. H. (2010). Synthesis of perindopril erbumine. Chemical World, 51 (9), 552-554.
Remko, M., Bojarska, J., Ježko, P., Sieroń, L., Olczak, A., & Maniukiewicz, W. (2011). Crystal and molecular structure of perindopril erbumine salt. Journal of Molecular Structure, 997 (1), 103-109.
