Fluvastatin

spinqualitylabelsall models Fluvastatin, also known as Lescol Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Better Known as: Lescol Marketed By: Novartis Major Indication: Hyperlipidemia & High Cholesterol (Hypercholesterolemia) Drug Class: HMGR Inhibitor or Statin Date of FDA Approval (Patent Expiration): 1993 (2011) 2000 Sales: $430 Million Importance: Was largely replaced by Lipitor. Statins are so ubiquitous, doctors have even suggested handing them out with fast food. See: the article See Pharmaceutical Drugs for more information about other drugs and disorders Mechanism of Action Fluvastatin is an inhibitor of HMG-CoA Reductase (HMGR), a highly regulated enzyme responsible for the committed step in cholesterol synthesis. Fluvastatin, like most of the statins, binds HMGR 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 Fluvastatin contribute to binding as well. These interactions help Fluvastatin outcompete HMG-CoA, the substrate of HMGR, in binding to HMGR.

Pharmacokinetics

Statin Hypercholesterolemia at 10mg Dosage Parameter HMGR (Lipitor) Fluvastatin (Lescol) Lipitor (Mevacor) Pharmaceutical Drugs (Zocor) HMG-CoA Reductase (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 66 320 50-90 Equivalent LDL Reduction Dosage (mg) 10 -- 80 20 5 -- Metabolism Hepatic (CYP3A4) Hepatic (CYP2C9) Hepatic (CYP3A4) Hepatic (CYP3A4) None Hepatic (CYP2C8) For References, See References

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