The methods of theoretical chemistry have been used to elucidate molecular properties of the antihypertensive, cardiovascular protective and antithrombotic perindopril ((2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid). The geometries and energies of various neutral and ionized complexes of perindopril erbumine and perindopril l-arginine have been computed using HF/6-31G(d) and Becke3LYP/6-31G(d) methods. The calculations showed that in both, the isolated state and water solution perindopril erbumine exists as a neutral complex. In the gas-phase perindopril l-arginine both neutral and ionic complexes are, at the HF level of theory, almost equally stable. The B3LYP level of theory slightly favors single proton transfer complex perindopril l-arginine (by about 14 kJ mol(-1)). In polar solvents like water, the ionized form of perindopril l-arginine becomes much more favored. According to our calculations l-arginine is bound to perindopril more strongly (by about 25 kJ mol(-1)) than erbumine.

Remko, M. (2009). Molecular structure and stability of perindopril erbumine and perindopril L-arginine complexes. European journal of medicinal chemistry, 44(1), 101-108.

Approximately 25% of US adults have high blood pressure (BP). Selection of effective and safe antihypertensive therapy for these individuals is an important health-care priority. High BP can be treated with a wide range of antihypertensive agents from a number of different classes. These drugs may differ in their suitability for administration to different subpopulations of patients. Results from both clinical trials and postmarketing surveillance indicate that the angiotensin-converting enzyme (ACE) inhibitor perindopril erbumine is safe and well tolerated in a wide range of patients with hypertension. Cough, the most common ACE inhibitor-associated side effect, is also the most common clinical adverse event reported for perindopril, but <2% of perindopril-treated patients discontinue therapy because of cough. Other adverse events often associated with ACE inhibitors, first-dose hypotension and hyperkalemia, appear to occur less often with perindopril than with other agents in this class. The favorable safety profile for perindopril extends to a wide range of patients, including the elderly and those with either heart failure or renal disease. Perindopril has no negative effects on lipids in patients with hyperlipidemia or on glycemic control in patients with type 2 diabetes mellitus, and it reduces proteinuria in patients with renal disease. Perindopril has no known clinically significant drug-drug interactions. Thus, perindopril is a safe BP-lowering agent with documented tolerability in a wide range of patients with hypertension.

Clark, L. T. (2001). Safety profile of perindopril. The American journal of cardiology, 88(7), 36-40.

The present study was performed to compare the bioavailability of two perindopril erbumine (CAS 107133-36-8) 4 mg tablet formulations (test formulation and reference formulation). This study was a randomized, single-blind, two-period, two-sequence cross-over study which included 20 healthy adult male and female subjects under fasting conditions. In this study, one subject withdrew from the study and one reserve subject did not appear at both periods. The pharmacokinetic parameters were assessed based on the concentrations of perindopril (CAS 82834-16-0) and perindoprilat (CAS 95153-31-4) because perindopril has litte pharmacologic activity until hydrolized in the liver into its active metabolite, perindoprilat.

Setiawati, E., Deniati, S. H., Yunaidi, D. A., Handayani, L. R., Santoso, I. D., Arland, J. A., ... & Lian, L. Y. (2011). Bioequivalence study of two perindopril erbumine tablet formulations in healthy volunteers. Arzneimittelforschung, 61(04), 234-238.