Carrier-mediated uptake of pravastatin by rat hepatocytes in primary culture

Biochem Pharmacol. 1992 Feb 18;43(4):667-70. doi: 10.1016/0006-2952(92)90228-b.


The transport mechanism of pravastatin, a new cholesterol-lowering drug, was compared in vitro with rat hepatocyte primary culture and mouse skin fibroblasts (L-cells). The uptake of 14C-labeled pravastatin by cultured hepatocytes was temperature- and dose-dependent. The temperature-dependent uptake as a function of [14C]pravastatin concentration showed saturation kinetics with Km = 32.2 microM and a maximal uptake rate of 68 pmol/mg protein/min. The uptake of pravastatin was inhibited significantly by metabolic inhibitors such as rotenone, oligomycin A, antimycin A, 2,4-dinitrophenol and KCN. Unlabeled pravastatin as well as R-416 and R-195, structural analogues of pravastatin, effectively competed for the hepatic uptake of [14C]pravastatin at 37 degrees. These results indicate that pravastatin is taken up by the liver by an active transport. In contrast, the transport of pravastatin by L-cells was temperature-independent and non-saturable, suggesting that the uptake of pravastatin by L-cells is mediated by passive diffusion. The marked difference in the uptake mechanism of pravastatin between hepatocytes and L-cells may account for a unique feature of this drug in that the uptake and inhibition of cholesterol biosynthesis occur selectively in the liver.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biological Transport, Active
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Kinetics
  • L Cells / drug effects
  • L Cells / metabolism
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Mice
  • Pravastatin / antagonists & inhibitors
  • Pravastatin / metabolism*
  • Pravastatin / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Temperature


  • Pravastatin