Once-daily pravastatin in patients with primary hypercholesterolemia: a dose-response study.
This multicenter, double-blind, placebo-controlled study was conducted to evaluate dose-response effects and safety of once-daily administration of pravastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Pravastatin 5, 10, 20, 40 mg or placebo was administered at bedtime to 150 patients with primary hypercholesterolemia inadequately controlled on a low-fat, low-cholesterol (AHA Phase I) diet. After 8 weeks of treatment, pravastatin produced dose-dependent reductions in low-density lipoprotein (LDL) cholesterol of 19.2 to 34.1% (p less than or equal to .001 vs. baseline and placebo) and reductions in total cholesterol of 14.3 to 25.1% (p less than or equal to .01 to p less than or equal to .001 vs. placebo and p less than or equal to .001 vs. baseline). The relationship between the loge dose of pravastatin and decrease in LDL cholesterol was linear (p less than 0.002). High-density-lipoprotein cholesterol increased up to 11.7% and triglycerides decreased by as much as 23.9%. Pravastatin was well tolerated; no patient withdrew from the study as a consequence of treatment-related adverse events. Despite its relatively short serum half-life of approximately 2 h, once-daily administration of pravastatin provides a safe and effective means of reducing elevated LDL and total cholesterol.
Jones
P H
PH
Baylor College of Medicine, Houston, Texas.
Farmer
J A
JA
Cressman
M D
MD
McKenney
J M
JM
Wright
J T
JT
Proctor
J D
JD
Berkson
D M
DM
Farnham
D J
DJ
Wolfson
P M
PM
Colfer
H T
HT
D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors*; D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D017035:Pravastatin; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D000214:Acyl Coenzyme A; D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D009281:Naphthalenes; D010919:Placebos; D014280:Triglycerides; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D002784:Cholesterol; D017035:Pravastatin