Tissue-selective action of pravastatin due to hepatocellular uptake via a sodium-independent bile acid transporter.
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.
Ziegler
K
K
Institut für Pharmakologie und Toxikologie, Giessen, Germany.
Stünkel
W
W
D000818:Animals; D000838:Anions; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D017035:Pravastatin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D000838:Anions; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D012964:Sodium; D017035:Pravastatin