Atorvastatin
From Proteopedia
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:Date of FDA Approval: 1996 <br /> | :Date of FDA Approval: 1996 <br /> | ||
:2009 Sales: $12.7 Billion <ref>http://www.forbes.com/2008/06/18/pfizer-ranbaxy-lipitor-biz-healthcare-cx_mh_0618bizpfizer.html</ref> | :2009 Sales: $12.7 Billion <ref>http://www.forbes.com/2008/06/18/pfizer-ranbaxy-lipitor-biz-healthcare-cx_mh_0618bizpfizer.html</ref> | ||
| + | :Why You Should Care: It is the best selling drug in the world. Statins are so ubiquitous, doctors have even suggested handing them out to everyone. See: [http://www.bbc.co.uk/news/health-10955522 the article] | ||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
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===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
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| + | |<div style='font-size:1.2em; text-align:center; padding-bottom:0.3em'>Parameter</div> | ||
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| + | Atorvastatin (Single 40mg Dose): vs Simvastatin (Zocor) (single 20mg Dose) <ref>PMID:12686673</ref> | ||
| + | Bioavailability (Systemic Availability): 14% (30%) vs | ||
| + | Cmax = 28.6 ng/ml | ||
| + | AUC = 205 ng*h/ml | ||
| + | T<sub>max</sub> 1hr vs 1.3hr | ||
| + | T<sub>1/2</sub> = 11.5 hr vs | ||
| - | + | IC-50: 154nM vs 66nM | |
| + | |||
| + | ===Effectiveness and Side Effects=== | ||
| + | ====Effectiveness== | ||
| + | Compared to the other statins, Atorvaststin is the most effective with typical reductions in LDL of 30-40% at the 10mg level. At 10mg, Atorvastatin reduces LDL about 2% more than 20mg Simvastatin. <ref>PMID:20456733</ref> | ||
| + | ====Side Effects==== | ||
| + | The most common side effects were nasopharyngitis (cold like symptoms) and Arthralgia (arthritis), occurring in about 7% of patients although not significantly higher than was seen with the placebo. As with all statyins, myopathy (muscle weakness) can also occur. <ref>http://www.rxlist.com/lipitor-drug.htm</ref> Interstingly, grapfruit juice can drastically increase the effect of statins, increasing AUC by as much as 1500%<ref>PMID:9585793</ref> | ||
===The Jist=== | ===The Jist=== | ||
THis is a wildly successful drug large in part becaues Pfizer is incredible at marketing its products... | THis is a wildly successful drug large in part becaues Pfizer is incredible at marketing its products... | ||
Revision as of 08:46, 9 November 2010
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Atorvastatin
Better Known as: Lipitor
- Marketed By: Pfizer, Inc.
- Major Indication: Hyperlipidemia & High Cholesterol (Hypercholesterolemia)
- Date of FDA Approval: 1996
- 2009 Sales: $12.7 Billion [1]
- Why You Should Care: It is the best selling drug in the world. Statins are so ubiquitous, doctors have even suggested handing them out to everyone. See: the article
Mechanism of Action
Atorvastatin is an inhibitor of HMG-CoA Reductase, a highly regulated enzyme responsible for the committed step in cholesterol synthesis. Atorvastatin 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 Atorvastatin contribute to binding as well.[2] These interactions help Atorvastatin outcompete outcompete HMG-CoA, the substrate of HMGR in binding to HMGR.[3]
Pharmacokinetics
Parameter
| asdf |
Atorvastatin (Single 40mg Dose): vs Simvastatin (Zocor) (single 20mg Dose) [4] Bioavailability (Systemic Availability): 14% (30%) vs Cmax = 28.6 ng/ml AUC = 205 ng*h/ml Tmax 1hr vs 1.3hr T1/2 = 11.5 hr vs
IC-50: 154nM vs 66nM
Effectiveness and Side Effects
==Effectiveness
Compared to the other statins, Atorvaststin is the most effective with typical reductions in LDL of 30-40% at the 10mg level. At 10mg, Atorvastatin reduces LDL about 2% more than 20mg Simvastatin. [5]
Side Effects
The most common side effects were nasopharyngitis (cold like symptoms) and Arthralgia (arthritis), occurring in about 7% of patients although not significantly higher than was seen with the placebo. As with all statyins, myopathy (muscle weakness) can also occur. [6] Interstingly, grapfruit juice can drastically increase the effect of statins, increasing AUC by as much as 1500%[7]
The Jist
THis is a wildly successful drug large in part becaues Pfizer is incredible at marketing its products...
References
- ↑ http://www.forbes.com/2008/06/18/pfizer-ranbaxy-lipitor-biz-healthcare-cx_mh_0618bizpfizer.html
- ↑ Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science. 2001 May 11;292(5519):1160-4. PMID:11349148 doi:10.1126/science.1059344
- ↑ Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res. 1995 Jan;31(1):9-27. PMID:7784310
- ↑ Lins RL, Matthys KE, Verpooten GA, Peeters PC, Dratwa M, Stolear JC, Lameire NH. Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients. Nephrol Dial Transplant. 2003 May;18(5):967-76. PMID:12686673
- ↑ Weng TC, Yang YH, Lin SJ, Tai SH. A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharm Ther. 2010 Apr;35(2):139-51. PMID:20456733 doi:10.1111/j.1365-2710.2009.01085.x
- ↑ http://www.rxlist.com/lipitor-drug.htm
- ↑ Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther. 1998 Apr;63(4):397-402. PMID:9585793 doi:10.1016/S0009-9236(98)90034-0
