Pharmacokinetics and pharmacodynamics of pravastatin alone and with cholestyramine in hypercholesterolemia

Clin Pharmacol Ther. 1990 Aug;48(2):201-7. doi: 10.1038/clpt.1990.136.

Abstract

The pharmacokinetics, pharmacodynamics, and safety of pravastatin, a new selective 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, were evaluated during monotherapy and with subsequent concomitant cholestyramine therapy in 33 patients with primary hypercholesterolemia in this randomized study. After 4 weeks, pravastatin monotherapy (5 mg, 10 mg, and 20 mg twice daily) significantly decreased total cholesterol by 17% to 24% (p less than 0.001 versus baseline) and low-density lipoprotein cholesterol by 23% to 35% (p less than 0.001). High-density lipoprotein cholesterol increased by 8% to 9%, and triglycerides decreased by 6% to 9%. The area under the serum concentration-time curve and maximum serum concentration of pravastatin showed dose-proportionality; time to maximum serum concentration and serum elimination half-life were independent of dose. When added to pravastatin therapy, cholestyramine enhanced the lipid-lowering effects of pravastatin. After 4 weeks of combination therapy, total cholesterol was reduced by 32% to 38% (p less than 0.001 versus baseline), and low-density lipoprotein cholesterol was reduced by 47% to 56% (p less than 0.001). High-density lipoprotein cholesterol increased by 11% to 18% (p less than 0.05). Pravastatin was well tolerated; no clinical adverse events directly attributable to the drug were reported.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Anticholesteremic Agents / pharmacokinetics*
  • Anticholesteremic Agents / pharmacology
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cholestyramine Resin / administration & dosage
  • Cholestyramine Resin / pharmacokinetics*
  • Cholestyramine Resin / pharmacology
  • Drug Therapy, Combination
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / pharmacokinetics*
  • Heptanoic Acids / pharmacology
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Male
  • Middle Aged
  • Naphthalenes / administration & dosage
  • Naphthalenes / pharmacokinetics*
  • Naphthalenes / pharmacology
  • Phospholipids / blood
  • Pravastatin
  • Randomized Controlled Trials as Topic
  • Triglycerides / blood

Substances

  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Heptanoic Acids
  • Naphthalenes
  • Phospholipids
  • Triglycerides
  • Cholestyramine Resin
  • Cholesterol
  • Pravastatin