Simvastatin: Difference between revisions
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* Date of FDA Approval (Patent Expiration): 1997 (2006)<br /> | * Date of FDA Approval (Patent Expiration): 1997 (2006)<br /> | ||
* 2005 Sales: $4.4 Billion <ref>http://money.cnn.com/2006/06/23/news/companies/zoloft_zocor/index.htm</ref> | * 2005 Sales: $4.4 Billion <ref>http://money.cnn.com/2006/06/23/news/companies/zoloft_zocor/index.htm</ref> | ||
* | * Importance: Zocor is one of the best selling drugs of all time and was the second best selling drug in 2005 before going off patent. Since statins are so ubiquitous, doctors have even suggested handing them out with fast food. See: [http://www.bbc.co.uk/news/health-10955522 the article] <br /> | ||
* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information | * The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information | ||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
Simvastatin is rapidly hydrolyzed ''in vivo'' to generate mevinolinic acid, a powerful inhibitor of [[HMG-CoA Reductase]] (HMGR). HMGR is a <scene name='Simvastatin/Just_simva_hmg/1'>highly regulated enzyme</scene> responsible for the committed step in cholesterol synthesis. Simvastatin, like other statins, <scene name='Simvastatin/Statin_simva/1'>binds HMGR</scene> via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Simvastatin help form the pocket the drug is positioned in.<ref>PMID:11349148</ref> These interactions help Simvastatin outcompete HMG-CoA, the substrate of HMGR, in binding to HMGR.<ref>PMID:7784310</ref> | Simvastatin is rapidly hydrolyzed ''in vivo'' to generate mevinolinic acid, a powerful inhibitor of [[HMG-CoA Reductase]] (HMGR). HMGR is a <scene name='Simvastatin/Just_simva_hmg/1'>highly regulated enzyme</scene> responsible for the committed step in cholesterol synthesis. Simvastatin, like other statins, <scene name='Simvastatin/Statin_simva/1'>binds HMGR</scene> via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Simvastatin help form the pocket the drug is positioned in.<ref>PMID:11349148</ref> These interactions help Simvastatin outcompete HMG-CoA, the substrate of HMGR, in binding to HMGR.<ref>PMID:7784310</ref> | ||
