[Atorvastatin (Lipitor): a review of its pharmacological and clinical profile].
Hypercholesterolemia is a major risk factor for the development of coronary heart disease. HMG-CoA reductase inhibitors have been used as first-line drugs because of both their superior cholesterol lowering effect and reliable safety profile. Since there are many patients whose plasma cholesterol level does not reach the therapeutic target even if reductase inhibitors are available, more effective drugs have been strongly required for a long time. Atorvastatin, one of the most recently introduced statins, produces greater plasma LDL-cholesterol reductions than other statins. This pronounced effect of atorvastatin seems to be due to its long-lasting action, presumably a reflection of longer residence time of atorvastatin and its active metabolites in the liver. Clinical trials of atorvastatin have also demonstrated marked plasma triglyceride reductions. The triglyceride reduction with atorvastatin seems to stem from the following two indirect mechanisms, limiting VLDL secretion from the liver and increase in clearance of triglyceride-rich lipoprotein via induced LDL receptors from plasma. Eleven clinical trials of atorvastatin, which have been developed in Japan, clearly demonstrated its ability to reduce LDL-C levels more strongly and in significantly more patients to LDL-C treatment goals than other reductase inhibitors with similar safety profiles. Therefore, atorvastatin adds a new dimension to the effective management of hypercholesterolemia and combined hyperlipidemia.
Applied Pharmacology Research Pharmacology Laboratory, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tukuba-shi, Ibaraki 305-8585, Japan. funatsu@yamanouchi.co.jp
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Funatsu
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Kakuta
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Tanaka
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Arai
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Suzuki
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Miyata
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000517:prevention & control; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000378:metabolism; D002986:Clinical Trials as Topic; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D006949:Hyperlipidemias / Q000188:drug therapy; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D011973:Receptors, LDL / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D011758:Pyrroles; D011973:Receptors, LDL; D014280:Triglycerides; D000069059:Atorvastatin