IN VITRO EVIDENCES FOR SIMVASTATIN AND LOSARTAN POTASSIUM INTERACTION AND ITS IN VIVO IMPLICATIONS

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Abstract

In the present paper, we describe the in vitro availability of simvastatin, a potent HMG-CoA reductase inhibitor, in presence of losartan potassium, which is a non-peptide angiotensin II receptor antagonist. These studies were carried out at 37, 48 and 60°C in different pH environments simulating human body compartments. The reactions were studied by UV spectroscopy and the availability of both drugs in presence of each other was determined by deriving a simultaneous equation for two component system through modifcation of Beer`s law. The interactions were further characterized by IR and H¹NMR spectroscopic techniques. It was observed that availability of simvastatin in presence of losartan at 37 ºC in simulated gastric juice, at pH 7.4 and pH 9.0 was blocked by losartan through the formation of a charge-transfer complex while the availability of losartan in turn was immensely increased. In pH 4.0 these effects were reversed, availability of simvastatin increased and the availability of losartan was depressed. Similar results were observed at higher temperatures.

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Most cited references 13

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Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study.

Sandeep R Das, Mark Drazner, Daniel L Dries … (2005)

The association between higher body mass index (BMI) and lower B-type natriuretic peptide (BNP) level is thought to be mediated by expression of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue. To explore this association, we tested 2 hypotheses: (1) that N-terminal (NT)-proBNP, which is not believed to bind NPR-C, would not be associated with BMI and (2) that lower BNP would be more closely associated with fat mass than with lean mass. Measurements of BNP, NT-proBNP, and body composition by direct dual energy x-ray absorptiometry (DEXA) were performed in 2707 subjects from the Dallas Heart Study. The associations between obesity and low BNP (<4 ng/L) or low NT-proBNP (lowest sex-specific quartile) were evaluated with multivariable logistic regression models stratified by sex and adjusted for age, race/ethnicity, hypertension, left ventricular mass, and end-diastolic volume. Higher BMI was independently associated with lower BNP and NT-proBNP (all P<0.001). When BMI was replaced with both DEXA-derived lean and fat mass, greater lean mass, but not fat mass, was associated with low BNP and NT-proBNP levels. In a large, population-based cohort, we confirm the previously described association between higher BMI and lower BNP and demonstrate a similar inverse association between BMI and NT-proBNP. Interestingly, both BNP and NT-proBNP are more closely associated with lean mass than with fat mass. These findings do not support the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via NPR-C.

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Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction (from The Heart Institute of Spokane Diet Intervention and Evaluation Trial).

Kevin R. Short, Douglas Bibus, Michael Shuler … (2008)

Whether a Mediterranean-style diet reduces cardiovascular events and mortality more than a low-fat diet is uncertain. The objectives of this study were to actively compare low-fat and Mediterranean-style diets after first myocardial infarction (MI) in a randomized, controlled clinical trial and to compare dietary intervention per se with usual care in a case-control analysis. First MI survivors were randomized to a low-fat (n = 50) or Mediterranean-style (n = 51) diet. The 2 diets were low in saturated fat ( 0.75% kcal). Participants received individual dietary counseling sessions, 2 within the first month and again at 3, 6, 12, 18, and 24 months, along with 6 group sessions. Combined dietary intervention groups (cases, n = 101) were compared with a usual-care group (controls, n = 101) matched for age, gender, MI type and treatment, and status of diabetes mellitus and hypertension. Primary-outcome-free survival (a composite of all-cause and cardiac deaths, MI, hospital admissions for heart failure, unstable angina pectoris, or stroke) did not differ between low-fat (42 of 50) and Mediterranean-style (43 of 51) diet groups over a median follow-up period of 46 months (range 18 to 72; log-rank p = 0.81). Patients receiving dietary intervention had better primary-outcome-free survival (85 of 101) than usual-care controls (61 of 101) (log-rank p <0.001), with unadjusted and adjusted odds ratios of 0.33 (95% confidence interval 0.18 to 0.60, p <0.001) and 0.28 (95% confidence interval 0.13 to 0.63, p = 0.002), respectively. In conclusion, active intervention with either a low-fat or a Mediterranean-style diet similarly and significantly benefits overall and cardiovascular-event-free survival after MI.

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Sudden Cardiac Death Among Firefighters ≤45 Years of Age in the United States

Justin Yang, Dennis Teehan, Andrea Farioli … (2013)

Sudden cardiac death (SCD) is the leading cause of death in firefighters. Although on-duty SCD usually occurs in older victims almost exclusively because of coronary heart disease, no studies have examined causation across the career span. In the present retrospective case-control study, cases of SCD in young (aged ≤45 years) firefighters from the National Institute for Occupational Safety and Health fatality investigations (n = 87) were compared with 2 age- and gender-matched control groups: occupationally active firefighters (n = 915) and noncardiac traumatic firefighter fatalities (n = 56). Of the SCD cases, 63% were obese and 67% had a coronary heart disease-related cause of death. The SCD victims had much heavier hearts (522 ± 102 g) than noncardiac fatality controls (400 ± 91 g, p 450 g) was found in 66% of the SCD victims and conveyed a fivefold increase (95% confidence interval [CI] 1.93 to 12.4) in SCD risk. Furthermore, hypertension, including cases with left ventricular hypertrophy, increased SCD risk by 12-fold (95% CI 6.23 to 22.3) after multivariate adjustment. A history of cardiovascular disease and smoking were also independently associated with elevated SCD risk (odds ratio 6.89, 95% CI 2.87 to 16.5; and odds ratio 3.53, 95% CI 1.87 to 6.65, respectively). In conclusion, SCD in young firefighters is primarily related to preventable lifestyle factors. Obesity entry standards, smoking bans, and improved screening and/or wellness program are potential strategies to reduce SCD in younger firefighters.