Tissue-selective action of pravastatin due to hepatocellular uptake via a sodium-independent bile acid transporter

Biochim Biophys Acta. 1992 Jul 7;1139(3):203-9. doi: 10.1016/0925-4439(92)90135-a.

Abstract

Pravastatin is a foreign substrate of a sodium-independent transport system for bile acids. The tissue selectivity of pravastatin in inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase is due to the uptake via a transport system which exists predominantly in liver cells. Pravastatin competitively inhibits the sodium-independent hepatocellular uptake of cholate, taurocholate and ouabain, whereas the total uptake of cholate is non-competitively blocked. The affinity of pravastatin to the sodium-dependent taurocholate transporter is, however, low. Millimolar concentrations of pravastatin are needed to inhibit the sodium-taurocholate cotransporter. Pravastatin has no affinity to other transport systems in liver cells such as those for long-chain fatty acids, amino acids, rifampicin and bivalent organic cations.

MeSH terms

  • Animals
  • Anions
  • Bile Acids and Salts / metabolism*
  • Biological Transport
  • Carrier Proteins / metabolism
  • Kinetics
  • Liver / metabolism*
  • Male
  • Molecular Structure
  • Pravastatin / chemistry
  • Pravastatin / metabolism
  • Pravastatin / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Sodium / metabolism

Substances

  • Anions
  • Bile Acids and Salts
  • Carrier Proteins
  • Sodium
  • Pravastatin