4843
T3D4788
Simvastatin
Simvastatin is a lipid-lowering agent that is derived synthetically from the fermentation of Aspergillus terreus. It is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol.
79902-63-9
54454
C25H38O5
White powder.
135-138°C
Insoluble
Absorption of simvastatin, estimated relative to an intravenous reference dose, in each of two animal species tested, averaged about 85% of an oral dose. In animal studies, after oral dosing, simvastatin achieved substantially higher concentrations in the liver than in non-target tissues. However, because simvastatin undergoes extensive first-pass metabolism, the availability of the drug in the systemic is low. Peak plasma concentration occurs 1.3 - 2.4 hours after administration.
Simvastatin is a prodrug in which the 6-membered lactone ring of simvastatin is hydrolyzed <i>in vivo</i> to generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol.
Hepatic, simvastatin is a substrate for CYP3A4. The major active metabolites of simvastatin are ‘_-hydroxyacid metabolite and its 6'-hydroxy, 6'-hydroxymethyl, and 6'-exomethylene derivatives
Route of Elimination: Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces.
Half Life: 3 hours
No indication of carcinogenicity to humans (not listed by IARC).
For the treatment of hypercholesterolemia and for the reduction in the risk of cardiac heart disease mortality and cardiovascular events. It can also be used in adolescent patients for the treatment of heterozygous familial hypercholesterolemia.
The most common adverse reactions that lead to discontinuation of therapy include gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%).
2014-09-11T05:16:36Z
2016-11-09T01:09:12Z
Simvastatin
9150
DB00641
true
[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)C(C)(C)CC
C25H38O5
InChI=1S/C25H38O5/c1-6-25(4,5)24(28)30-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-19-13-18(26)14-22(27)29-19/h7-8,11,15-16,18-21,23,26H,6,9-10,12-14H2,1-5H3/t15-,16-,18+,19+,20-,21-,23-/m0/s1
RYMZZMVNJRMUDD-HGQWONQESA-N
418.5662
418.271924326
Exogenous
Solid
4.68
HMDB05007
CHEMBL1064
49179
<p>Shieh-Shung J. Chen, Byron H. Arison, “Process for the preparation of 3-keto, 5-hydroxy simvastatin analogs.” U.S. Patent US4965200, issued April, 1981.</p>
CHEM003745