Therapeutic substitution post‐patent expiry: the cases of ace inhibitors and proton pump inhibitors
This paper examines whether there is a switch in total (originator and generic) consumption after generic entry from molecules that face generic competition towards other molecules of the same class, which are still in‐patent. Data from six European countries for the time period 1991 to 2006 are used to study the cases of angiotensin‐converting enzyme inhibitors and proton pump inhibitors. Empirical evidence shows that patent expiry of captopril and enalapril led to a switch in total (off‐patent originator and generic) consumption towards other in‐patent angiotensin‐converting enzyme inhibitors, whereas patent ex...
Source: Health Economics - May 21, 2013 Category: Health Management Authors: Sotiris Vandoros Tags: Health Economics Letter Source Type: research

Abstract 232: Parenteral Antihypertensive Use on the First Day of Hospitalization after Acute Ischemic Stroke: A US Population Study [Poster Session II]
Introduction: Elevated blood pressure (BP) is associated with increased risk of neurologic decline and poor outcome in acute ischemic stroke (AIS). The American Stroke Association (ASA) recommends antihypertensive (AH) therapy if BP is>220/120 mmHg, with a goal of 15-25% reduction in the first 24 hours. In thrombolytic candidates, BP should be maintained ≤185/110 mmHg for 24 hours after rt-PA. Labetalol and nicardipine are the recommended parenteral (IV) agents. We sought to characterize the use of IV AHs in the first 24 hours after AIS admission, stratified by treatment with rt-PA.Methods: This analysis utilized the...
Source: Circulation: Cardiovascular Quality and Outcomes - May 15, 2013 Category: Cardiology Authors: Wang, Y., McDonough, E., Adeoye, O., LaPensee, K., Crothers, T. C., Kleindorfer, D. Tags: Poster Session II Source Type: research

Superior renoprotective effects of the combination of breviscapine with enalapril and its mechanism in diabetic rats
Abstract: Breviscapine is a flavonoid extracted from a Chinese herb Erigeron breviscapus, previously it was shown that treatment with breviscapine attenuated renal injury in the diabetic rats. The purpose of this study was to investigate whether breviscapine combined with enalapril (an ACE inhibitor) have superior renoprotective effects against diabetic nephropathy. Rats were randomly separated into five groups: control, diabetes, diabetes treated with enalapril, diabetes treated with breviscapine, or diabetes treated with combined enalapril with breviscapine. Twenty-four hours urinary AER and the levels of 3-NT in renal t...
Source: Phytomedicine - May 13, 2013 Category: Drugs & Pharmacology Authors: Xing-Xin Xu, Wei Zhang, Pei Zhang, Xiang-Ming Qi, Yong-Gui Wu, Ji-Jia Shen Tags: Diabetes and endocrinology Source Type: research

Sex differences in angiotensin-converting enzyme modulation of Ang (1-7) levels in normotensive WKY rats.
Abstract BACKGROUND: Levels of the vasodilatory peptide angiotensin (Ang) (1-7) have been reported to be greater in females than in males, although the molecular mechanism responsible for this is unknown. Angiotensin-converting enzyme (ACE), ACE2, and neprilysin are key enzymes regulating Ang (1-7) formation. We conducted a study to determine the effect of sex on the activities of ACE, ACE2, and neprilysin in the kidneys of normotensive rats. We hypothesized that greater ACE2 or neprilysin activity in females would result in enhanced Ang (1-7) formation as compared with that in males. METHODS: We measured the...
Source: American Journal of Hypertension - May 1, 2013 Category: Cardiology Authors: Bhatia K, Zimmerman MA, Sullivan JC Tags: Am J Hypertens Source Type: research

Use of enteric coated mycophenolate sodium in adult resistant nephrotic syndrome.
Abstract Introduction: Treatment of patients with resistant/relapsed adult nephrotic syndrome (RNS) caused by glomerulopathies has no consensus therapy. Objectives: This is a retrospective analysis (RA), performed on 55 patients with RNS treated during one year with enteric coated sodium mycophenolate (EC-MPS) and reduced corticosteroids doses. Material and methods: Inclusion criteria for this RA were: patients aged ≥ 18 years old, diagnosed with RNS with histologically proven glomerulopathy who had received standard therapy with enalapril and/or losartan and 10 mg per day or 20 mg of prednisone every other day...
Source: Clinical Nephrology - April 23, 2013 Category: Urology & Nephrology Authors: Nadal MA, Lococo B, Fazzini MB, Gonzalez G, Otero AB, Malvar AV Tags: Clin Nephrol Source Type: research

Enalapril and Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction in Patients With Malignant Hemopathies: The OVERCOME Trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies)
This study sought to evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction (LVSD) in patients with hematological malignancies.Background: Current chemotherapy may induce LVSD. Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy.Methods: In this randomized, controlled study, 90 patients with recently diagnosed acute leukemia (n = 36) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation (HSCT) (n = 54) and without LVSD wer...
Source: Journal of the American College of Cardiology - April 12, 2013 Category: Cardiology Authors: Xavier Bosch, Montserrat Rovira, Marta Sitges, Ariadna Domènech, José T. Ortiz-Pérez, Teresa M. de Caralt, Manuel Morales-Ruiz, Rosario J. Perea, Mariano Monzó, Jordi Esteve Tags: Cardiac Imaging in Heart Failure Source Type: research

Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: role of fasudil, a Rho kinase inhibitor
This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure (MAP) and renal function were determined in conscious animals pretreated with enalapril (250 mg/l in drinking water) for 1 wk to block the endogenous renin-angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100 ng·kg–1·min–1) induced a greater increase in MAP and renal vascular resistance a...
Source: AJP: Renal Physiology - April 1, 2013 Category: Urology & Nephrology Authors: Ojeda, N. B., Royals, T. P., Alexander, B. T. Tags: ARTICLES Source Type: research

Enalapril mitigates focal alveolar lesions, a histological marker of late pulmonary injury by radiation to the lung.
Abstract The goal of our study was to identify a histological marker for testing countermeasures for mitigation of late radiation injury to the lung. Pulmonary fibrosis is currently the best described "late effect" in survivors of acute radiation pneumonitis. However, robust fibrosis does not develop in some rodent strains for years after a single dose of radiation to the whole thorax. We observed radiation-associated focal alveolar lesions that were rich in giant cells and macrophages containing cholesterol clefts in the lungs of irradiated WAG/RijCmcr rats. These lesions were first observed after pneum...
Source: Radiation Research - April 1, 2013 Category: Physics Authors: Gao F, Narayanan J, Joneikis C, Fish BL, Szabo A, Moulder JE, Molthen RC, Jacobs ER, Rao RN, Medhora M Tags: Radiat Res Source Type: research

Effects of enalapril on the expression of cardiac angiotensin-converting enzyme and angiotensin-converting enzyme 2 in spontaneously hypertensive rats.
Abstract BACKGROUND: The discovery of angiotensin-converting enzyme 2 (ACE2) has greatly modified understanding of the renin-angiotensin system (RAS). AIMS: To investigate the cardiac expression of ACE2 and ACE in spontaneously hypertensive rats (SHRs) and the effects of enalapril on them. METHODS: Fifteen SHRs were randomly assigned to two groups: an SHR control group (n=7), treated with vehicle; and an enalapril group (n=8), treated with enalapril (15mg/kg/day). After 4weeks of treatment, the rats were killed and the left ventricular tissue was dissected. Reverse transcription-polymerase chain reaction and Weste...
Source: Archives of Cardiovascular Diseases - April 1, 2013 Category: Cardiology Authors: Yang Z, Yu X, Cheng L, Miao LY, Li HX, Han LH, Jiang WP Tags: Arch Cardiovasc Dis Source Type: research

PKPD modeling of the interrelationship between mean arterial blood pressure, cardiac output and total peripheral resistance in conscious rats
Conclusions and ImplicationsA system‐specific model characterizing the interrelationship between BP, CO and TPR has been obtained, which can be used to quantify and predict cardiovascular drug effects and to elucidate the MoA for novel compounds. Ultimately, the proposed PKPD model may allow prediction of BP effects in humans based on preclinical data. (Source: British Journal of Pharmacology)
Source: British Journal of Pharmacology - March 21, 2013 Category: Drugs & Pharmacology Authors: N. Snelder, B.A. Ploeger, O. Luttringer, D.F. Rigel, R.L. Webb, D. Feldman, F. Fu, M. Beil, L. Jin, D.R. Stanski, M. Danhof Tags: Research Paper Source Type: research

Effect of ipsilateral ureteric obstruction on contralateral kidney and role of renin angiotensin system blockade on renal recovery in experimentally induced unilateral ureteric obstruction
Conclusions: Considerable injury is also inflicted to the contralateral normal kidney while ipsilateral kidney remains obstructed. Use of RAS blocking drugs has been found to significantly improve renal recovery on the contralateral kidney. It can, thus, be postulated that contralateral renal parenchymal injury was mediated through activation of RAS. (Source: Journal of Indian Association of Pediatric Surgeons)
Source: Journal of Indian Association of Pediatric Surgeons - March 21, 2013 Category: Surgery Authors: Shasanka S PandaMinu BajpaiAnand SinhaSaumyaranjan MallickMehar C Sharma Source Type: research

Randomized Controlled Trial of Enalapril on Decline in Glomerular Filtration Rate and Proteinuria in Children with Chronic Kidney Disease.
Abstract OBJECTIVE: To evaluate the efficacy of enalapril with no enalapril treatment on decline in glomerular filtration rate and reduction in proteinuria in children with chronic kidney disease (CKD). Design: Open label, randomized controlled trial. Setting: Pediatric nephrology clinic at a tertiary care referral hospital. INTERVENTION: Children with GFR between 15-60 mL/min/1.73 m2 were randomized to receive either enalapril at 0.4 mg/kg /day or no enalapril for 1 year. OUTCOME MEASURES: Primary outcomes: Change in GFR using 99mTc-DTPA and urine protein to creatinine ratio. Secondary outcome...
Source: Indian Pediatrics - March 5, 2013 Category: Pediatrics Authors: Hari P, Sahu J, Sinha A, Pandey RM, Bal CS, Bagga A Tags: Indian Pediatr Source Type: research

From the Editor
The research papers in this issue begin with the laboratory-based study of Ushijima and colleagues in Wistar rats in whom they studied clock genes following administration of propranolol or atenolol. They observed a direct effect of the beta blockers on the clock genes in the heart rather than in the central nervous system. These findings could have important therapeutic implications for the use of beta adrenergic blocking agents in the treatment of myocardial ischemia. Der Sarkissian and associates studied the mechanisms of regression of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). They fou...
Source: Journal of the American Society of Hypertension - February 18, 2013 Category: Cardiology Authors: Myron H. Weinberger Tags: Editorial Source Type: research

Evaluation of enalapril affecting the renin-angiotensin system in normal and stress-induced rats based on urinary metabolites of amines and cortisol
Conclusion: It can be speculated that enalapril prevented stress-induced increases of adrenergic, serotonergic and cortical mechanisms. (Source: Journal of the Renin-Angiotensin-Aldosterone System : JRAAS)
Source: Journal of the Renin-Angiotensin-Aldosterone System : JRAAS - February 15, 2013 Category: Biomedical Science Authors: Kumar, K. A., Satyanarayana, S., Kumar, K. E. Tags: Articles Source Type: research

Role of angiotensin II type 2 receptor during regression of cardiac hypertrophy in spontaneously hypertensive rats
Abstract: We previously reported that the AT1 receptor antagonist valsartan and the angiotensin converting enzyme (ACE) inhibitor enalapril decrease DNA synthesis and stimulate apoptosis in interstitial fibroblasts and epicardial mesothelial cells during regression of ventricular hypertrophy in spontaneously hypertensive rats (SHR). To examine the role of the AT2 receptor in this model, we studied hearts from SHR treated with valsartan or enalapril either alone or combined with the AT2 antagonist PD123319 for 1 or 2 weeks. Apoptosis was evaluated by quantification of DNA fragmentation or by TUNEL labeling. At 1 week, valsa...
Source: Journal of the American Society of Hypertension - February 14, 2013 Category: Cardiology Authors: Shant Der Sarkissian, Bun-Seng Tea, Rhian M. Touyz, Denis deBlois, Taben M. Hale Tags: Research Articles Source Type: research

Roles played by 20-HETE, angiotensin II and endothelin in mediating the hypertension in aging female spontaneously hypertensive rats
This study aimed to determine the roles of three of the systems known to contribute to HT in animal studies: angiotensin II (ANG II; enalapril inhibitor), eicosanoids [1-aminobenzotriazole (1-ABT) inhibitor], and endothelin (ETA receptor antagonist), on blood pressure (BP) in three groups of female spontaneously hypertensive rats (SHR), aged 18 mos (postmenopausal rat, PMR). After baseline telemetry BP, three drug periods were performed for 5 days each: single blockade (ABT or enalapril), double blockade (ABT+enalapril or enalapril+ABT), and triple blockade (all 3 drugs). Controls received no treatment until the third peri...
Source: AJP: Regulatory, Integrative and Comparative Physiology - February 1, 2013 Category: Physiology Authors: Lima, R., Yanes, L. L., Davis, D. D., Reckelhoff, J. F. Tags: Hormones, Reproduction and Development Source Type: research

The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats.
In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects. PMID: 23369979 [PubMed - as supplied by publisher] (Source: Braz J Med Biol Res)
Source: Braz J Med Biol Res - February 1, 2013 Category: Research Authors: Dalpiaz PL, Lamas AZ, Caliman IF, Medeiros AR, Abreu GR, Moyses MR, Andrade TU, Alves MF, Carmona AK, Bissoli NS Tags: Braz J Med Biol Res Source Type: research

Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: Role of fasudil, a Rho kinase inhibitor.
This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure and renal function were determined in conscious animals pretreated with enalapril (250mg/l in drinking water) for one week to block the endogenous renin angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100ng/kg/min) induced a greater increase in mean arterial pressure (MAP) and renal vascular resistance and enhanc...
Source: American Journal of Physiology. Renal Physiology - January 23, 2013 Category: Physiology Authors: Ojeda NB, Royals TP, Alexander BT Tags: Am J Physiol Renal Physiol Source Type: research

Endothelium-Derived Nitric Oxide Supports Renin Cell Recruitment Through the Nitric Oxide-Sensitive Guanylate Cyclase Pathway [Original Articles]
This study aimed to define the role of nitric oxide (NO) with regard to the recruitment pattern of renin-producing cells and to the possible pathways along which NO could act. We considered the hypothesis that endothelium-derived NO acts via NO-sensitive guanylate cyclase. Mice were treated with low-salt diet in combination with the angiotensin I–converting enzyme inhibitor enalapril for 3 weeks, which led to a 13-fold increase in renin expression associated with marked recruitment of renin cells in afferent arterioles and hypertrophy of the juxtaglomerular apparatus in wild-type mice. In wild-type mice additionally ...
Source: Hypertension - January 16, 2013 Category: Cardiology Authors: Neubauer, B., Machura, K., Kettl, R., Lopez, M. L. S. S., Friebe, A., Kurtz, A. Tags: Original Articles Source Type: research

Enalapril Reduces Proliferation and Hyaluronic Acid Release in Orbital Fibroblasts
Thyroid Jan 2013, Vol. 23, No. 1: 92-96. (Source: Thyroid)
Source: Thyroid - January 4, 2013 Category: Endocrinology Tags: article Source Type: research

Pharmacokinetics, Pharmacodynamics, and Tolerability of ACT-077825, a New Direct Renin Inhibitor After Multiple-ascending Doses in Healthy Subjects
This study was conducted to characterize the multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ACT-077825, a new direct renin inhibitor, in healthy male subjects. In this single-center, double-blind, placebo-controlled, active-controlled (20 mg of enalapril), randomized multiple-ascending dose study, ACT-077825 was administered once a day. for 7 days in the 50–1000 mg dose range to sodium- and potassium-restricted subjects. ACT-077825 pharmacokinetics on days 1 and 7 were characterized by dose-proportional increases in Cmax and AUCτ. At steady state, accumulation was modest (1.5- to 1.7-fold)....
Source: Journal of Cardiovascular Pharmacology - January 1, 2013 Category: Cardiology Tags: Original Article Source Type: research

Nilotinib-associated acute pancreatitis.
CONCLUSIONS: This case demonstrates a possible association between acute pancreatitis and nilotinib use. Although a rare phenomenon, clinicians should be alert for signs and symptoms of pancreatitis, as treatment with nilotinib for CML is becoming more common. PMID: 23300151 [PubMed - in process] (Source: The Annals of Pharmacotherapy)
Source: The Annals of Pharmacotherapy - January 1, 2013 Category: Drugs & Pharmacology Authors: Engel T, Justo D, Amitai M, Volchek Y, Mayan H Tags: Ann Pharmacother Source Type: research

Influence of different types of commercially available microcrystalline cellulose on degradation of perindopril erbumine and enalapril maleate in binary mixtures / Vpliv različnih tipov komercialno dostopne mikrokristalne celuloze na razpad erbuminijevega perindoprilata in enalaprilijevega maleata v binarnih zmeseh.
eza A Abstract Influence of some commercially available types of microcrystalline cellulose (MCC) on the stability of certain active pharmaceutical ingredients (APIs), when in contact, has been investigated. Two structurally similar APIs, perindopril erbumine (PER) and enalapril maleate (EM), both well-known angiotensin-converting enzyme inhibitors were used. The main properties of an MCC that could determine the stability for each API were measured and correlated to the stability of these two APIs in binary mixtures. The stability of these APIs differed when in contact with different types of MCC. The dominant pr...
Source: Acta Pharmaceutica - December 1, 2012 Category: Drugs & Pharmacology Authors: Vehovec T, Gartner A, Planinšek O, Obreza A Tags: Acta Pharm Source Type: research

Effects of Angiotensin-Converting Enzyme Inhibitory Peptide LAP on Vascular Remodeling.
Abstract The aim of this article is to study the efficiency of an angiotensin-converting enzyme (ACE)-inhibitory peptide LAP on the blood pressure (BP) and the vascular remodeling in spontaneously hypertensive rats (SHRs). Ten-week-old male SHRs were divided into four groups with 10 animals in each group and treated for 2 months: blank, pseudo-experimental (NS), enalapril (ENA), and LAP. The alterations of BP, plasma angiotensin II (AngII) levels, and morphological changes of left common carotid artery and the third level of superior mesenteric artery were investigated. After 2 weeks of treatment, LAP an...
Source: Clinical and Experimental Hypertension - November 30, 2012 Category: Cardiology Authors: Huang J, Luo M, Fang H, Zheng H, Shen Y, Li L, Deng Y, Xu H Tags: Clin Exp Hypertens Source Type: research

Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: Insights from the SOLVD Treatment trial
Abstract: Background: Angiotensin-converting enzyme inhibitors improve outcomes in systolic heart failure (SHF). However, doubts linger about their effect in SHF patients with chronic kidney disease (CKD).Methods: In the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial, 2569 ambulatory chronic HF patients with left ventricular ejection fraction ≤35% and serum creatinine level ≤2.5mg/dl were randomized to receive either placebo (n=1284) or enalapril (n=1285). Of the 2502 patients with baseline serum creatinine data, 1036 had CKD (estimated glomerular filtration rate (Source: International Journal of Cardiology)
Source: International Journal of Cardiology - January 18, 2012 Category: Cardiology Authors: C. Barrett Bowling, Paul W. Sanders, Richard M. Allman, William J. Rogers, Kanan Patel, Inmaculada B. Aban, Michael W. Rich, Bertram Pitt, Michel White, George C. Bakris, Gregg C. Fonarow, Ali Ahmed Tags: Original Articles Source Type: research