Extending therapy options in treating lipid disorders: a clinical review of cerivastatin, a novel HMG-CoA reductase inhibitor.
Cerivastatin is a third generation pure enantiomeric HMG-CoA reductase inhibitor. It reduces low density lipoprotein (LDL)-cholesterol by 22 to 44% at doses of 0.1 to 0.8 mg/day. The drug has been extensively evaluated for more than 5 years in clinical trials and is currently marketed in a number of countries at doses of 0.1 to 0.3 mg/day. Cerivastatin has been tested in more than 4000 patients during extensive phase II and III studies. About 40% of patients in these trials were women, and many participants were aged between 65 and 75 years. The trial populations had moderate to severe hypercholesterolaemia, with mean baseline LDL-cholesterol levels of approximately 5.2 mmol/L (200 mg/dl). In large phase III trials, cerivastatin, over the dosage range of 0.1 to 0.4 mg/day, reduced LDL-cholesterol by 22.4 to 36.1% from baseline. As with other HMG-CoA reductase inhibitors, the log-linear dose-response curve of cerivastatin showed a 6% additional decrease in mean LDL-cholesterol levels for each doubling of the daily dose, with no plateau effect noted at the highest dosage yet tested (0.8 mg/day). High density lipoprotein cholesterol levels increased by 4 to 10% during cerivastatin therapy. This effect, which was consistent with that of other HMG-CoA reductase inhibitors, was not dose related. As has been found with other statins, the triglyceride-lowering effects of cerivastatin are dependent on baseline triglyceride levels, with very small reductions occurring in patients with low initial levels [< 1.7 mmol/L (150 mg/dl)], and larger dose-dependent reductions of up to 36% with the 0.4 mg/day dose observed in patients with baseline triglyceride levels >2.8 mmol/L (250 mg/dl). Cerivastatin was well tolerated in all studies. Cerivastatin recipients and recipients of other HMG-CoA reductase inhibitors experienced a similar incidence of adverse events (including hepatic transaminase elevations) in comparative studies. Cerivastatin is an effective and safe lipid-lowering agent for most patients with hypercholesterolaemia.
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Medical Research Laboratories, Highland Heights, Kentucky 41076, USA.
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C086276:cerivastatin