Lovastatin
|
Better Known as: Mevacor
- Marketed By: Merck & Co.
- Major Indication: Hyperlipidemia & High Cholesterol (Hypercholesterolemia)
- Drug Class: HMGR Inhibitor or Statin
- Date of FDA Approval (Patent Expiration): 1991 (2001)
- 2000 Sales: $520 Million
- Why You Should Care: Was the first HMG-CoA Inhibitor. Statins are so ubiquitous, doctors have even suggested handing them out with fast food. See: the article
- The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information
Mechanism of Action
Lovastatin is rapidly hydrolyzed in vivo into its corresponding b-hydroxyacid, which is an inhibitor of HMG-CoA Reductase (HMGR), a highly regulated enzyme responsible for the committed step in cholesterol synthesis. Lovastatin outcompetes HMG-CoA, the substrate of HMGR, in binding to HMGR.[1]
Pharmacokinetics
| Statin Pharmacokinetics at 10mg Dosage.[2][3][4][5][6][7] | ||||||
|---|---|---|---|---|---|---|
| Parameter | Atorvastatin (Lipitor) | Fluvastatin (Lescol) | Lovastatin (Mevacor) | Simvastatin (Zocor) | Rosuvastatin (Crestor) | Cerivastatin (Baycol) |
| Tmax (hr) | 2.5 | 1 | 3 | 1.5 | 4 | 1.5 |
| Cmax (ng/ml) | 27-66 | 448 | 10-20 | 7.3 | 4.34 | 3.43 |
| Bioavailability (%) | 12 | 19-29 | 5 | 5 | 20 | 60 |
| Protein Binding (%) | 80-90 | 99 | 95 | 95 | 88 | 99 |
| T1/2 (hr) | 15-30 | 2 | 3 | 2.7 | 19 | 2.2 |
| AUC (ng/ml/hr) | 104 | ~150 | 33 | 125 | 48 | 14.5 |
| IC50 (nM) | 154 | 198 | 800-4200 | 66 | 320 | 50-90 |
| Equivalent LDL Reduction Dosage (mg) | 10 | -- | 80 | 20 | 5 | -- |
| Metabolism | Hepatic (CYP3A4) |
Hepatic (CYP2C9) |
Hepatic (CYP3A4) |
Hepatic (CYP3A4) |
Not Metabolized |
Hepatic (CYP2C8) |
References
- ↑ Corsini A, Maggi FM, Catapano AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res. 1995 Jan;31(1):9-27. PMID:7784310
- ↑ Park JW, Siekmeier R, Lattke P, Merz M, Mix C, Schuler S, Jaross W. Pharmacokinetics and pharmacodynamics of fluvastatin in heart transplant recipients taking cyclosporine A. J Cardiovasc Pharmacol Ther. 2001 Oct;6(4):351-61. PMID:11907637
- ↑ Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation. 2004 Jun 15;109(23 Suppl 1):III50-7. PMID:15198967 doi:10.1161/01.CIR.0000131519.15067.1f
- ↑ 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
- ↑ Kiser JJ, Gerber JG, Predhomme JA, Wolfe P, Flynn DM, Hoody DW. Drug/Drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers. J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):570-8. PMID:18176327 doi:10.1097/QAI.0b013e318160a542
- ↑ Li P, Callery PS, Gan LS, Balani SK. Esterase inhibition by grapefruit juice flavonoids leading to a new drug interaction. Drug Metab Dispos. 2007 Jul;35(7):1203-8. Epub 2007 Apr 23. PMID:17452418 doi:10.1124/dmd.106.013904
- ↑ Renders L, Haas CS, Liebelt J, Oberbarnscheidt M, Schocklmann HO, Kunzendorf U. Tacrolimus and cerivastatin pharmacokinetics and adverse effects after single and multiple dosing with cerivastatin in renal transplant recipients. Br J Clin Pharmacol. 2003 Aug;56(2):214-9. PMID:12895195