Clinical pharmacokinetics of statins

Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):457-81.

Abstract

This article reviews the pharmacokinetic properties of HMG-CoA reductase inhibitors (or statins), as reported in humans. Most data presented here refer to commercially available statins (atorvastatin, fluvastatin, lovastatin and simvastatin), although statins that have recently been withdrawn (cerivastatin) or are currently under development (glenvastatin, pitavastatin and rosuvastatin) will also be considered. All statins with the exception of pitavastatin show very low systemic bioavailability due to an extensive first pass effect at the intestinal and/or hepatic level. Such a characteristic can be advantageous, since the liver is the target organ for statins. Unlike most statins, lovastatin and simvastatin are administered as inactive lactone prodrugs. Statins differ mainly in the degree of metabolism and the number of active and inactive metabolites. All statins but pravastatin show highly active metabolites, the pharmacological activity depending on the kinetic profile of both parent compound and active metabolites. Pravastatin has the lowest protein binding (50% vs. > 90%) and is eliminated by both metabolism and renal excretion. Atorvastatin shows the longest terminal half-life (11-14 h vs. 1-3 h). Pharmacokinetic interactions with statins are very likely to occur, particularly for those statins that are CYP3A4 substrates. However, although of extreme interest in clinical practice, this subject was extensively reviewed in a previous article and therefore is not discussed here.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Administration, Oral
  • Age Factors
  • Anticholesteremic Agents / pharmacokinetics
  • Anticholesteremic Agents / therapeutic use
  • Biological Availability
  • Clinical Trials as Topic
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Sex Factors

Substances

  • Anticholesteremic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors