Benazepril

Webb, Randy L.; Miller, D. Douglas; Traina, Vincent M.; Gómez, Héctor W.

doi:10.1111/j.1527-3466.1990.tb00432.x

Cited by 27 publications

(20 citation statements)

References 40 publications

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“…Benazepril, enalapril, imidapril, and ramipril are currently approved for use in dogs with CHF. Benazepril hydrochloride (Fortekor ® ; Novartis Animal Health, Basel, Switzerland) is a nonsulfhydryl prodrug which is converted in vivo by esterases into its active metabolite, benazeprilat, a highly potent and selective inhibitor of ACE (Webb 1990) with well-documented effectiveness in symptomatic canine CHF (King et al 1995;Lefebvre et al 2007). In the BENCH (BENazepril in Canine Heart Disease) Study Group (1999), the mean survival time of benazepril-treated dogs with mild to moderate CHF was improved by a factor of 2.7, as compared with the placebo group (428 vs. 158 days, p < 0.05).…”

Section: Benazepril Markedly Influences the Dynamics Of The Circulatimentioning

confidence: 99%

Chronobiology and Pharmacologic Modulation of the Renin–Angiotensin–Aldosterone System in Dogs: What Have We Learned?

Mochel

Danhof

2015

Reviews of Physiology, Biochemistry and Pharmacology Vol. 169

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Congestive heart failure (CHF) is a primary cause of morbidity and mortality with an increasing prevalence in human and canine populations. Recognition of the role of renin-angiotensin-aldosterone system (RAAS) overactivation in the pathophysiology of CHF has led to significant medical advances. By decreasing systemic vascular resistance and angiotensin II (AII) production, angiotensin-converting enzyme (ACE) inhibitors such as benazepril improve cardiac hemodynamics and reduce mortality in human and dog CHF patients. Although several experiments have pointed out that efficacy of ACE inhibitors depends on the time of administration, little attention is paid to the optimum time of dosing of these medications. A thorough characterization of the chronobiology of the renin cascade has the potential to streamline the therapeutic management of RAAS-related diseases and to help determining the optimal time of drug administration that maximizes efficacy of ACE inhibitors, while minimizing the occurrence of adverse effects. We have developed an integrated pharmacokinetic-pharmacodynamic model that adequately captures the disposition kinetics of the paradigm drug benazeprilat, as well as the time-varying changes of systemic renin-angiotensin-aldosterone biomarkers, without and with ACE inhibition therapy. Based on these chronobiological investigations, the optimal efficacy of ACE inhibitors is expected with bedtime dosing. The data further show that benazepril influences the dynamics of the renin-angiotensin-aldosterone cascade, resulting in a profound decrease in AII and aldosterone (ALD), while increasing renin activity for about 24 h. From the results of recent investigations in human, it is hypothesized that reduction of AII and ALD is one of the drivers of increased survival and improved quality of life in dogs receiving ACE inhibitors. To support and consolidate this hypothesis, additional efforts should be directed toward the collection of circulating RAAS peptides in spontaneous cases of canine CHF. If such a link could be established, profiling of these biomarkers could support determination of the severity of heart failure, complement clinical and echocardiographic findings, and be used for therapeutic drug monitoring purposes.

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Section: Benazepril Markedly Influences the Dynamics Of The Circulatimentioning

confidence: 99%

Chronobiology and Pharmacologic Modulation of the Renin–Angiotensin–Aldosterone System in Dogs: What Have We Learned?

Mochel

Danhof

2015

Reviews of Physiology, Biochemistry and Pharmacology Vol. 169

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“…Many ACE inhibitors have been developed, and some are now in use in veterinary medicine. Benazepril (BP) is a new orally active and long acting ACE inhibitor without a sulfhydryl group [11,12,18]. The biological action of benazepril is considered to be exerted through benazeprilat, its active metabolite.…”

mentioning

confidence: 99%

Efficacy of Monotherapy with Benazepril, an Angiotensin Converting Enzyme Inhibitor, in Dogs with Naturally Acquired Chronic Mitral Insufficiency.

et al. 1997

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ABSTRACT. Benazepril (BP), an angiotensin convertive enzyme inhibitor, was administered orally once daily for 4 weeks to 31 dogs with mild to moderate (NYHA functional classes II and III) congestive heart failure caused from mitral insufficiency (MI). There were no significant changes in clinical signs, electrocardiogram findings, radiographical observations and plasma biochemical results in 11 dogs treated with placebo for 4 weeks. In 31 dogs treated with BP, appetite increased, and mean scores of heart failure signs, such as activity, exercise tolerance, cough and respiratory effort, were significantly improved. No dog displays signs suggesting systemic hypotension. One dog died suddenly on the 26th day of treatment with BP. This dog had good vigor and appetite till the evening before the death, and cough and exercise tolerance had been gradually improving. The heart rate and ECG parameters of BP treated dogs did not change significantly, but length of long axis of the heart decreased. In plasma biochemical tests, plasma urea nitrogen (UN) levels did not change significantly, and plasma creatinine (CRE) levels increased slightly within the normal ranges during BP trial. Two dogs had higher plasma UN levels with slightly higher plasma CRE levels, but had normal general condition and other biochemical results. Plasma ACE activity decreased to 57.3% of pre-treatment level at 4 weeks after BP treatment. It is concluded that BP monotherapy was efficacious at least in dogs with relatively low grade congestive heart failure caused by MI. -KEY WORDS: ACE inhibitor, benazepril, canine, congestive heart failure, mitral insufficiency.

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“…These changes include a decrease in erythrocytic parameters, an increase in serum urea nitrogen, a decrease in heart weight, and hyperplasia of the juxtaglomerular cells. Also the maternotoxic and fetotoxic effects observed in the rabbit segment II reproduction study are typical of ACE inhibitors and are well documented in the literature (14,27,41).…”

Section: Toxicologymentioning

confidence: 63%

Preclinical Profile of Zofenopril: An Angiotensin Converting Enzyme Inhibitor with Peculiar Cardioprotective Properties

Subissi

Evangelista

Giachetti

1999

Cardiovascular Drug Reviews

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Benazepril

Cited by 27 publications

References 40 publications

Chronobiology and Pharmacologic Modulation of the Renin–Angiotensin–Aldosterone System in Dogs: What Have We Learned?

Chronobiology and Pharmacologic Modulation of the Renin–Angiotensin–Aldosterone System in Dogs: What Have We Learned?

Efficacy of Monotherapy with Benazepril, an Angiotensin Converting Enzyme Inhibitor, in Dogs with Naturally Acquired Chronic Mitral Insufficiency.

Preclinical Profile of Zofenopril: An Angiotensin Converting Enzyme Inhibitor with Peculiar Cardioprotective Properties

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