Disease relevance of Zofenopril

• Zofenopril after anterior myocardial infarction [1].
• Hydralazine and zofenopril reduced mean arterial pressure comparably (W, 106 +/- 23 versus H, 81 +/- 12 versus Z, 84 +/- 18 mm Hg, P = .002) yet had a differential effect on the ratio of left ventricular weight to body weight (W, 3.9 +/- 0.5 versus H, 3.3 +/- 0.4 versus Z, 2.4 +/- 0.2 g/kg, P < .005) [2].
• Zofenopril plus hydrochlorothiazide: Combination therapy for the treatment of mild to moderate hypertension [3].
• STUDY OBJECTIVE--The aim was to compare the effects of two novel angiotensin converting enzyme (ACE) inhibitors, spirapril and zofenopril, on cardiac remodelling in rats with congestive heart failure after myocardial infarction [4].
• Among many new ACE inhibitors being developed, compounds eliminated via hepatic routes, such as fosfenopril and zofenopril, may prove advantageous in renal failure [5].

Psychiatry related information on Zofenopril

• In conclusion, zofenopril/HCTZ 30/12.5 mg/day provides more optimal BP control in a larger proportion of patients than would be achievable with monotherapy, while maintaining the tolerability profile observed with each individual agent, and thereby potentially enhancing patient compliance [3].
• Conversely the prevalence of severe CHF (1.6% vs 2.6%: risk reduction 55.5%; 95% confidence interval 9 to 63; p = 0.0325) and the combined occurrence of death or severe CHF (4.8% vs 8.2%: risk reduction 59%; 95% confidence interval 11 to 71; p = 0.024) were reduced after 6 weeks of treatment with zofenopril [6].

High impact information on Zofenopril

• The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators [7].
• In contrast, therapy with zofenopril was associated with a 50% increase in total heart rate variability (p = 0.09) and a significant (p = 0.03) twofold increase in high frequency heart rate variability, indicating a significant augmentation of parasympathetic tone [8].
• No significant changes occurred in heart rate, cardiac output, and blood pressure at rest, and zofenopril did not result in haemodynamic alterations during exercise [9].
• Twenty-one clinically stable patients with coronary artery disease or cardiomyopathy completed a randomized double-blind treatment period of 2 months with either 15 mg zofenopril once daily or placebo [9].
• Zofenopril significantly increased mean stroke volume at rest from 59 to 67 ml (48 vs 48 ml in the control group, 95% confidence interval of the difference 1 to 16 ml) and left ventricular ejection fraction at rest from 39 to 43% (30 vs 30% in the control group, 95% confidence interval of the difference 1 to 8%) [9].

Chemical compound and disease context of Zofenopril

• CONCLUSIONS: In rats with renovascular hypertension and hypertensive heart disease that included LVH and fibrosis, equipotent doses of ZOF, NIF, and LAB normalized arterial pressure associated with regression of LVH while only ZOF and NIF were found to regress myocardial fibrosis [10].
• Neither zofenopril nor captopril, however, had any effect on coronary flow before or after ischemia [11].
• These data suggest that the cardioprotective effect of zofenopril and captopril is independent of hemodynamic changes or reduction of the toxicity of oxygen free radicals and that it could be related to a reduction in release of NE [12].
• CONCLUSIONS: The SMILE-2 study demonstrates that both zofenopril and lisinopril are safe and associated with a rather low rate of severe hypotension when given in accordance with a dose-titrated scheme to thrombolyzed patients with acute MI [13].

Biological context of Zofenopril

• Systemic blood pressure was acutely reduced by zofenopril, and severe but reversible hypotension occurred in 15% of hospitalized patients and in 3% of those treated over the long term [14].
• Left ventricular size decreased and ejection fraction (EF) increased in patients who received zofenopril, and the improvement was greater among patients with poorer ventricular function (EF less than 40%) [14].
• Extraction ratios (E) for zofenopril by the gut, liver, and lungs were calculated based on the ratios of the area under the curve (AUC) values of zofenopril in arterial plasma after administration by the various routes [15].
• Fosinopril and zofenopril had the greatest inhibitory potency (IC50 values of 55 and 81 microM, respectively) while the other ACE inhibitors exhibited low-affinity interactions with the renal peptide transporter [16].
• Two hours after oral administration of 7.5 mg of zofenopril we observed a decrease in blood pressure, heart rate, and forearm vascular resistance along with an increase in venous distensibility [17].

Anatomical context of Zofenopril

• The SH-containing angiotensin-converting enzyme (ACE) inhibitors zofenopril and captopril have been shown to protect the ischemic myocardium independently of ACE inhibition [18].
• Zofenopril has been reported to cause relaxation in aortic smooth muscle rings via an endothelium-dependent component [18].
• Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species [19].
• Compared to zofenopril-treated rabbits, arterial sections of the placebo-group had significant increase in the intimal presence of macrophages-derived foam cells (p < 0.05), ox-LDL (p < 0.01), and native LDL (p < 0.01) detected by immunocytochemistry with RAM-11, MDA2 and NP1533975 monoclonal antibodies, respectively [20].
• In the placebo-treated group, platelet radioactivity was 0.52+/-0.12 equivalent of radioactivity per mg of tissue in the common carotid and 0.25+/-0.18 in the abdominal aorta; in contrast, rabbits treated by zofenopril had 0.20+/-0.12 in the common carotid and 0.06+/-0.01 in the abdominal aorta [20].

Associations of Zofenopril with other chemical compounds

• The haemodynamic effects of the sulfhydryl-containing angiotensin converting enzyme inhibitor, zofenopril, were studied in patients in New York Heart Association functional class II and III [9].
• In clinical trials comparing zofenopril/HCTZ with each agent administered as monotherapy, combination therapy was more effective in normalising BP [3].
• Zofenoprilat, the active form of zofenopril, significantly and dose dependently reduced the intracellular reactive oxygen species (ROS) and superoxide formation induced by oxidized low-density lipoprotein (ox-LDL) (P <.001) and tumor necrosis factor-alpha (TNF-alpha) (P <.001) [19].
• Atenolol reduced blood pressure (BP) by 0 +/- 6/8 +/- 2 mm Hg (ns/P < 0.01), and zofenopril by 14 +/- 4/6 +/- 2 (P < 0.01/P < 0.01), not significantly different between the two agents [21].
• The effects of chronic treatment with the new sulfhydryl angiotensin-converting enzyme (ACE)-inhibitor, zofenopril, in comparison with the classical sulfhydryl ACE-inhibitor captopril or enalapril or placebo on the development of atherosclerosis were determined in apolipoprotein-E knockout (apoE(-/-)) mice [22].

Gene context of Zofenopril

• The lipid peroxidation, protein oxidation, and nitric oxide levels as well as xanthine oxidase and myeloperoxidase activities were increased and the catalase and superoxide dismutase activities were decreased in the IR group; zofenopril treatment prevented these changes (p <0.05) [23].
• The cardioprotective activity of 100 microM zofenopril was abolished by both KATP blockers [18].
• We conclude that oral acute zofenopril administration, in patients with congestive heart failure, causes an arterial and venous forearm vasodilatation which is probably involved in the acute changes in plasma levels of ANF and AVP observed after drug administration [17].
• The aim of the present study was to evaluate the importance of a history of HBP on the clinical efficacy of early treatment with the angiotensin-converting enzyme (ACE) inhibitor zofenopril in patients with anterior AMI [24].
• Zofenopril administration was followed by a dose-dependent inhibition of in vitro ACE activity (7.5 mg, 65%; 15 mg, 89%; 30 mg, 94.5%) and a progressive increase in plasma active renin [25].

Analytical, diagnostic and therapeutic context of Zofenopril

• Rats were divided into 4 experimental groups: (a) control, (b) IR (60 min of ischemia followed by 24 hr of reperfusion), (c) zofenopril (15 mg/kg/day for 2 days), and (d) zofenopril+IR [23].
• The role of zofenopril in myocardial protection during cardioplegia arrest: an isolated rat heart model [26].
• METHODS: This phase III, double-blind, parallel-group, multicenter study compared the safety and efficacy of zofenopril and lisinopril in 1024 thrombolyzed patients with acute MI [13].
• Assay of zofenopril and its active metabolite zofenoprilat by liquid chromatography coupled with tandem mass spectrometry [27].

References