Lipid-lowering drugs of the statin. Is a prodrug from which the body is formed during the hydrolysis active form, rendering lipid-lowering effect. Lowers blood cholesterol, LDL, VLDL, triglycerides and moderately increase the content of HDL (antiatherogenic).
The mechanism of action of simvastatin, as well as other statins, mainly associated with the violation of cholesterol synthesis in the liver at the stage of mevalonic acid by reversible inhibition of HMG-CoA reductase inhibitors. Reduction of cholesterol in the liver leads to an increase in the number of LDL receptors in the liver and increase their activity.
Simvastatin and other statins may inhibit the progression of atherosclerosis beyond their effects on LDL. Many explanations have been proposed, for example its inhibitory effect on macrophages in the atherosclerotic plaque lesions.
With the simultaneous use of simvastatin with cytostatics, fibrates, nicotinic acid in high doses, erythromycin, itraconazole, increasing the likelihood of myopathy. Simvastatin enhances the effect of indirect anticoagulants.
After oral administration, simvastatin is well absorbed from the gastrointestinal tract (85% on average). Cmax achieved within 4 hours Reception just before eating low fat does not affect the pharmacokinetic parameters of simvastatin.
In the "first pass" through the liver with the formation of simvastatin biotransformed active beta-metabolites. Plasma protein binding is 95%.
The concentration of the active metabolite of simvastatin in human systemic circulation is less than 5%.
Excreted unchanged and as metabolites, mainly in the bile - 60-85% 10-15% - in the form of inactive metabolites excreted by the kidneys.
Primary hypercholesterolemia in ineffectiveness of diet, combined hypercholesterolemia and hypertriglyceridemia.
Individual. The initial dose is 5-20 mg. If necessary, increase the dose every 4 weeks. Simvastatin take 1 time / evening. The maximum dose is 40 mg /
For patients receiving immunosuppressive drugs, the recommended starting dose is 5 mg / and the maximum dose - 5 mg /
In severe renal insufficiency (creatinine clearance below 30 ml / min) the initial dose is 5.10 mg /