Simvastatin: the clinical profile.
Simvastatin is the second in the class of compounds known as hydroxy-methylglutaryl-coenzyme A reductase inhibitors to be extensively studied in humans. The drug has now been given to over 1,800 patients with primary hypercholesterolemia for periods of up to two years. In the range of dosage from 10 to 40 mg once daily, therapy is associated with reductions of up to 30 percent in total cholesterol and 40 percent in low-density lipoprotein cholesterol levels, as well as with increases of approximately 10 percent in high-density lipoprotein cholesterol levels. The most common clinical adverse experiences are mild gastrointestinal effects and headache, which seldom require discontinuation of therapy. Elevations of creatine kinase (skeletal muscle isoenzyme) levels to more than three times the upper limit of the normal range have been seen in about 3 percent of patients, but also have seldom required discontinuation of therapy. Conversely, elevations of hepatic transaminase levels to more than three times the upper limit of the laboratory normal range have been seen in about 1.5 percent of patients and have caused discontinuation of therapy in 0.6 percent of patients treated. Simvastatin appears to be an effective and well-tolerated agent for the treatment of primary hypercholesterolemia and, as further study confirms long-term safety and efficacy, it should become a useful addition to the therapeutic armamentarium.
Walker
J F
JF
Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065.
D000368:Aged; D003402:Creatine Kinase / Q000097:blood; D004359:Drug Therapy, Combination; D005123:Eye / Q000187:drug effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000201:enzymology; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects; D008148:Lovastatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019821:Simvastatin; D000637:Transaminases / Q000097:blood
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D019821:Simvastatin; D000637:Transaminases; D003402:Creatine Kinase