Description
Simvastatin is a competitive inhibitor of HMG-CoA reductase (K
i = 0.12 nM). Simvastatin reduces plasma cholesterol levels in rats and dogs when administered at doses of 1.2 and 8 mg/kg, respectively. Simvastatin suppresses TNF-induced NF-κB activation (IC
50 =
~13 μM) and potentiates apoptosis in human myeloid leukemia cells. It also inhibits glutathione peroxidase 4 (GPX4) activity, increases malondialdehyde (MDA) levels, and induces ferroptosis in MDA-MB-231 and MCF-7 breast cancer cells. Formulations containing simvastatin have been used in the treatment of dyslipidemias.
Uses
Simvastatin Hydroxy Acid Sodium Salt is a metabolite of Simvastatin (S485000), a synthetic derivative of a fermentation product of Aspergillus terreus. A competitive inhibitor of HMG-CoA reductase. A synthetic analog of Lovastatin. Antilipemic. Simvastatin, the drug, is sold under the trade name Zocor.
in vitro
previous study found that simvastatin could inhibit the incorporation of 14c-acetate to 14c-sterol with an ic50 value of 15 nm in cultured hep g2 cells. in addition, simvastatin was found to be a potent inhibitor of cholesterol synthesis in cultured liver cells, whereas pravastatin inhibited cholesterol synthesis in liver cells only after these cells had been digested by collagenase [1].
in vivo
animal study showd that rats orally dosed with simvastatin had lower plasma cholesterol levels after 4 days of treatment. at the level of 0.02% of the diet, simvastatin lowered plasma cholesterol levels in rats by 64%. moreove, in dogs, simvastatin at a daily oral dosage of 8 mg/kg lower levels of plasma cholesterol. at this dosage, simvastatin was slightly more potent than lovastatin and the levels of plasma cholesterol in these dogs returned to pretreatment levels after stopping the treatment [1].
References
[1] chao, y. ,chen, j.s.,hunt, v.m., et al. lowering of plasma cholesterol levels in animals by lovastatin and simvastatin. european journal of clinical pharmacology 40, s11-s14 (1991).
[2] s martande s, kumari m, pradeep ar, pal singh s, kumar suke d. ncomparative evaluation of efficacy of subgingivally delivered 1.2% atorvastatin and 1.2% simvastatin in the treatment of intrabony defects in chronic periodontitis: a randomized controlled trial. j dent res dent clin dent prospects. 2017 winter;11(1):18-25.
