Reduce cholesterol synthesis results in a compensatory increase in uptake of plasma cholesterol mediated by an increase in the number of LDL receptors. Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3… It is also used to decrease the risk of heart problems in those at high risk. Clinically relevant pleiotropic effects of statins: drug properties or effects of profound cholesterol reduction? In this randomized, double-blind, controlled study, patients were treated with Simvastatin 20 mg/day or placebo. In addition, a 2010 study indicates that statins play a small role in lowering triglyceride levels and raising HDL (good) cholesterol. These drugs differ with respect to mechanism of action and to the degree and type of lipid lowering. In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with standard care, including diet, and either Simvastatin 20 to 40 mg/day (n=2,221) or placebo (n=2,223) for a median duration of 5.4 years. Patients had a mean age of 64 years (range 40 to 80 years), were 97% Caucasian and were at high risk of developing a major coronary event because of existing CHD (65%), diabetes (Type 2, 26%; Type 1, 3%), history of stroke or other cerebrovascular disease (16%), peripheral vessel disease (33%), or hypertension in males ≥65 years (6%). Avoid taking with >20 mg Simvastatin (or 40 mg for patients who have previously taken 80 mg Simvastatin chronically, e.g., for 12 months or more, without evidence of muscle toxicity), (Mean % Change Averaged at Weeks 18 and 24), Multi-Center Combined Hyperlipidemia Study, Table 6: Six-week, Lipid-lowering Effects of Simvastatin in Type IV Hyperlipidemia Median Percent Change (25, Patients should be advised about substances they should not take concomitantly with Simvastatin. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol.  |  The beneficial effects of statins are the result of their capacity to reduce cholesterol biosyntesis, mainly in the liver, where they are selectively distributed, as well as to the modulation of lipid metabolism, derived from their effect of inhibition upon HMG-CoA reductase. Find NCBI SARS-CoV-2 literature, sequence, and clinical content: Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation product of Aspergillus terreus. In a 72-week carcinogenicity study, mice were administered daily doses of Simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively (as total inhibitory activity based on AUC) after an 80 mg oral dose. The co-primary study endpoints were mean change per-patient in minimum and mean lumen diameters, indicating focal and diffuse disease, respectively. A second two-year rat carcinogenicity study with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). In a double-blind, placebo-controlled study, 175 patients (99 adolescent boys and 76 post-menarchal girls) 10 to 17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (HeFH) were randomized to Simvastatin (n=106) or placebo (n=67) for 24 weeks (base study). The Heart Protection Study (HPS) was a large, multi-center, placebo-controlled, double-blind study with a mean duration of 5 years conducted in 20,536 patients (10,269 on Simvastatin 40 mg and 10,267 on placebo). Taves, Minimization: a new method of assigning patients to treatment and control groups. We comply with the HONcode standard for trustworthy health information -, Dosage and Administration, Restricted Dosing for 80 mg (2.2), Patients with Homozygous Familial Hypercholesterolemia (2.4). HHS National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. The increased incidence of thyroid neoplasms appears to be consistent with findings from other statins. Bioavailability: 5% Onset of action: >3 days.
2020 simvastatin mechanism of action