The effect of CS-514 on serum lipids and apolipoproteins in hypercholesterolemic subjects.
CS-514 is a metabolic product of compactin and has a potent cholesterol-lowering effect in vitro and in animal studies by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The efficacy and adverse effects of the agent were studied in 41 hypercholesterolemic subjects by administering daily doses of 5, 20, or 40 mg for four weeks under double-blind conditions. Mean total serum cholesterol level was reduced by 11.1% in the 5-mg group, 18.8% in the 20-mg group, and 25.3% in the 40-mg group. Marked reduction of total serum cholesterol level was also observed in heterozygous familial hypercholesterolemics. Mean low-density lipoprotein cholesterol level and apolipoprotein B concentration decreased by 38.5% and 28.8%, respectively, in the 40-mg group, while high-density lipoprotein cholesterol level increased by 11.8%. No serious clinical and laboratory abnormalities were observed. Plasma cortisol and testosterone levels were not significantly affected. These results suggest that CS-514 will be a useful agent in the treatment of nonfamilial and heterozygous familial hypercholesterolemia.
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001053:Apolipoproteins / Q000097:blood*; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D017035:Pravastatin
D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D006538:Heptanoic Acids; D008055:Lipids; D009281:Naphthalenes; D017035:Pravastatin