87269-97-4Relevant articles and documents
Stress degradation studies of ramipril by a validated stability-indicating liquid chromatographic method
De Diego,Godoy,Mennickent,Olivares,Godoy
, p. 450 - 453 (2010)
Ramipril is an angiotensin-converting enzyme inhibitor which has chemical structure susceptible to degradation, therefore in this work forced degradation studies of ramipril were carried out by a developed and validated stability-indicating liquid chromat
Two validated stability-indicating chromatographic methods for the separation of two anti-hypertensive combinations in the presence of their degradation products or impurities
Samy Mostafa, Noha,AbdElHamid, Ghada,Elsayed Zaazaa, Hala,Mohamed Amer, Sawsan
, p. 2427 - 2439 (2019/07/16)
Two RP-HPLC methods were developed, optimized, and validated for the determination of two different anti-hypertensive combinations in the presence of their degradation products or impurities and in their pharmaceutical formulations. The first mixture is Ramipril (RAM) in combination with Amlodipine besylate (AML) [mixture I], while the second one is a combination of Ramipril (RAM), Atorvastatin (ATV), and Aspirin (ASP) [mixture II].The proposed combinations were successfully separated on X-bridge C18column (250 × 4.6?mm i.d, 5?μm p.s.), using a mobile phase of 0.05?M phosphate buffer-acetonitrile-THF (60:40:0.1% by volume) pH 2.5 and an isocratic mobile phase formed of acetonitrile-0.05?M phosphate buffer-THF (60:40:0.1% by volume) pH 2.5 for mixture (I) and (II) at a flow rate of 1?mL/min and 1.2?mL/min, respectively. The compromising components of the mixtures were detected at 218?nm. For the best separation of the mentioned components different parameters were examined and optimized. The two suggested methods were validated in compliance with the ICH guidelines and were successfully applied for the quantification of the cited components in presence of their obtained degradation products as well as in their commercial pharmaceutical formulations. For both methods the obtained results were statistically analyzed and compared to those of the official and reported methods; using Student’s t test and F test showing no significant difference with high accuracy and good precision.
In vitro drug metabolism by human carboxylesterase 1: Focus on angiotensin-converting enzyme inhibitors
Thomsen, Ragnar,Rasmussen, Henrik B.,Linnet, Kristian
, p. 126 - 133 (2014/01/06)
Carboxylesterase 1 (CES1) is the major hydrolase in human liver. The enzyme is involved in the metabolism of several important therapeutic agents, drugs of abuse, and endogenous compounds. However, no studies have described the role of human CES1 in the activation of two commonly prescribed angiotensinconverting enzyme inhibitors: enalapril and ramipril. Here, we studied recombinant human CES1-and CES2-mediated hydrolytic activation of the prodrug esters enalapril and ramipril, compared with the activation of the known substrate trandolapril. Enalapril, ramipril, and trandolapril were readily hydrolyzed by CES1, but not by CES2. Ramipril and trandolapril exhibited Michaelis-Menten kinetics, while enalapril demonstrated substrate inhibition kinetics. Intrinsic clearances were 1.061, 0.360, and 0.02 ml/min/mg protein for ramipril, trandolapril, and enalapril, respectively. Additionally, we screened a panel of therapeutic drugs and drugs of abuse to assess their inhibition of the hydrolysis of p-nitrophenyl acetate by recombinant CES1 and human liver microsomes. The screening assay confirmed several known inhibitors of CES1 and identified two previously unreported inhibitors: the dihydropyridine calcium antagonist, isradipine, and the immunosuppressive agent, tacrolimus. CES1 plays a role in the metabolism of several drugs used in the treatment of common conditions, including hypertension, congestive heart failure, and diabetes mellitus; thus, there is a potential for clinically relevant drug-drug interactions. The findings in the present study may contribute to the prediction of such interactions in humans, thus opening up possibilities for safer drug treatments. Copyright
Captopril inhibits the oxidative modification of apolipoprotein B-100 caused by myeloperoxydase in a comparative in vitro assay of angiotensin converting enzyme inhibitors
Van Antwerpen, Pierre,Legssyer, Ilham,Zouaoui Boudjeltia, Karim,Babar, Sajida,Moreau, Patrick,Moguilevsky, Nicole,Vanhaeverbeek, Michel,Ducobu, Jean,Neve, Jean
, p. 31 - 36 (2007/10/03)
The oxidative modification of low-density lipoproteins (LDL) is a key event in the formation of atheromatous lesions. Indeed, oxidized derivatives accumulate in the vascular wall and promote a local inflammatory process which triggers the progression of the atheromatous plaque. Myeloperoxidase (MPO) has been mentioned as a major contributor to this oxidative process. It takes part in the oxidation both of lipids by chlorination and peroxidation and of apolipoprotein B-100. Based on recent observations with several anti-inflammatory and thiol-containing drugs, the present study was designed to test the hypothesis that anti-hypertensive agents from the angiotensin converting enzyme (ACE) inhibitors group inhibit the oxidative modifications of Apo B-100 caused by MPO. Captopril, ramipril, enalapril, lisinopril and fosinopril were assessed by measuring: their inhibiting effect on the MPO / H2O2 / Cl- system, the accumulation of compound II, which reflects the inhibition of the synthesis of HOCl and the LDL oxidation by MPO in presence of several concentrations of ACE inhibitors. Only captopril, a thiol-containing ACE inhibitor, was able to significantly decrease the oxidative modification of LDL in a dose dependent manner and this by scavenging HOCl. This efficient anti-hypertensive drug therefore appears to also protect against the atherosclerotic process by this newly documented mechanism.
Rapid conversion of the new angiotensin converting enzyme inhibitor ramipril to its active metabolite in rats
Tabata,Yamazaki,Ohtake,Hayashi
, p. 865 - 867 (2007/10/02)
The rate of conversion of ramipril (Hoe 498), a new angiotensin converting enzyme (ACE) inhibitor, to its active metabolite was compared with that of enalapril. After intravenous administration to rats, ramipril was very rapidly desterified to its active moiety, ramiprilat. The ratio of the active metabolite level to the prodrug level in plasma at 5 min after administration was 10.7 for ramipril, which was about 5 times the ratio for enalapril. The in vitro conversion rates of ramipril were higher than those of enalapril in all rat tissue homogenates examined, including the liver, a main site of metabolism. The apparent Km values of ramipril and enalapril in the liver were 190 and 710 μmol/l, respectively, suggesting that ramipril has a higher affinity for esterase than enalapril. In conclusion, ramipril was superior to enalapril in efficiency of conversion to the active metabolite.