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Fluvastatin
- indication:To be used as an adjunct to dietary therapy to prevent cardiovascular events. May be used as secondary prevention in patients with coronary heart disease (CHD) to reduce the risk of requiring coronary revascularization procedures, for reducing progression of coronary atherosclerosis in hypercholesterolemic patients with CHD, and for the treatment of primary hypercholesterolemia and mixed dyslidipidemia.
- pharmacologypharmacology:
- mechanism: Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis. Inhibition results in a decrease in hepatic cholesterol levels which stimulates the synthesis of LDL receptors and increases hepatic uptake of LDL cholesterol. The end result is decreased levels of plasma total and LDL cholesterol.
- toxicity: Generally well-tolerated. May cause GI upset (diarrhea, nausea, constipation, gas, abdominal pain), myotoxicity (mypothy, myositis, rhabdomyolysis), and hepatotoxicity.
- absorprion: Rapidly and almost completely absorbed (> 90%), but undergoes extensive first pass metabolism. Bioavailability is 24% (range 9-50%).
- halflife: 1-3 hours
- roouteelimination: Fluvastatin is metabolized in the liver, primarily via hydroxylation of the indole ring at the 5- and 6-positions. In vitro studies demonstrated that fluvastatin undergoes oxidative metabolism, predominantly via 2C9 isozyme systems (75%). No significant (<6%) renal excretion of fluvastatin occurs in humans.
- volumedistribution: * 0.35 L/kg
- clearance: * 0.8 L/h/kg * 107 +/- 38.1 L/h [Hypercholesterolemia patients receiving a single dose of 20 mg] * 87.8 +/- 45 L/h [Hypercholesterolemia patients receiving 20 mg twice daily] * 108 +/- 44.7 L/h [Hypercholesterolemia patients receiving 40 mg single] * 64.2 +/- 21.1 L/h [Hypercholesterolemia patients receiving 40 mg twice daily]