Fluvastatin (sodium salt hydrate)

Fluvastatin is an inhibitor of HMG-CoA reductase (K_i = 0.3 nM for the rat enzyme) that binds to the HMG-CoA binding site.^1,2 It also inhibits the human cytochrome P450 (CYP) isoform CYP2C9 (IC₅₀ = 100 nM).³ Fluvastatin (2 mg/kg per day) inhibits increases in serum cholesterol, triglycerides, phospholipids, and thiobarbituric acid-reactive substances (TBARS) levels, as well as vascular angiotensin converting enzyme (ACE) activity in rabbits fed a high-cholesterol diet.⁴ It increases survival in a mouse model of myocardial infarction when administered at a dose of 10 mg/kg per day.⁵ Formulations containing fluvastatin have been used in the treatment of hypercholesterolemia and the prevention of cardiovascular disease.

1.Istvan, E.S., and Deisenhofer, J.Structural mechanism for statin inhibition of HMG-CoA reductaseScience292(5519)1160-1164(2001) 2.Corsini, A., Maggi, F.M., and Catapano, A.L.Pharmacology of competitive inhibitors of HMG-CoA reductasePharmacol. Res.31(1)9-27(1995) 3.Transon, C., Leemann, T., and Dayer, P.In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitorsEur. J. Clin. Pharmacol.50(3)209-215(1996) 4.Mitani, H., Bandoh, T., Ishikawa, J., et al.Inhibitory effects of fluvastatin, a new HMG-CoA reductase inhibitor, on the increase in vascular ACE activity in cholesterol-fed rabbitsBr. J. Pharmacol.119(6)1269-1275(1996) 5.Hayashidani, S., Tsutsui, H., Shiomi, T., et al.Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarctionCirculation105(7)868-873(2002)