Cerivastatin: a cellular and molecular drug for the future?

• Published in: Cellular and molecular life sciences : CMLS Vol. 60; no. 1; pp. 144 - 164
• Main Author: Siegel-Axel, D I
• Format: Journal Article
• Language: English
• Published: Switzerland Springer Nature B.V 01.01.2003; Birkhäuser Verlag
• Subjects: Alzheimer's disease; Angiotensin II - drug effects; Animals; Anticholesteremic Agents - therapeutic use; Arteriosclerosis - drug therapy; Bioavailability; Cardiovascular disease; Cellular biology; Endothelium, Vascular - drug effects; Enzymes; Epoprostenol - metabolism; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia - drug therapy; Hyperlipidemias - drug therapy; Hypolipidemic Agents - therapeutic use; Molecular biology; Monocytes - drug effects; Monocytes - metabolism; Muscle, Smooth, Vascular - drug effects; Neovascularization, Physiologic - drug effects; Osteoporosis; Pharmacokinetics; Pharmacology; Pyridines - adverse effects; Pyridines - pharmacology; Pyridines - therapeutic use; Receptors, Angiotensin - drug effects; Review; Statins; Thrombosis - drug therapy
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s000180300010

The 'statin story' began in 1987 when the first-generation, fungal HMG-CoA reductase inhibitor lovastatin received FDA approval in the USA. Ten years later, the sixth compound of this class came onto the world market--the fully synthetic statin cerivastatin. A number of clinical studies had confirmed its high pharmacological efficacy, its excellent pharmacokinetic properties with fast and nearly complete absorption after oral uptake, a linear kinetic over a broad concentration range, and its favorable safety profile. The greatest advantages, of cerivastatin, however, are its lipophilicity, its high bioavailability of about 60% after oral application and its potency at 100-fold lower doses compared to other lipophilic statins. Nevertheless, the most exciting findings are certainly its non-lipid-related, pleiotropic effects at the cellular and molecular level. Statin therapy was also found to reduce mortality in cases where cholesterol levels or atherosclerotic plaque formation remained unaltered. However, cerivastatin improves endothelial dysfunction, possesses anti-inflammatory, antioxidant, anticoagulant, antithrombotic, antiproliferative, plaque-stabilizing, immunmodulatory, and angiogenic effects, and may even prevent tumor growth, Alzheimer's disease, and osteoporosis. Most of these effects seem to be based on the inhibition of isoprenoid synthesis. Although cerivastatin is no longer on the market because of some problematic side effects, it could be one of the most potent cellular and molecular drugs for the future.