Effects of organic anions and bile acid conjugates on biliary excretion of pravastatin in the rat.
OBJECTIVE
Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, a so-called canalicular multispecific organic anion transporter (cMOAT). As there appear to be many canalicular organic anion transports, we examined the effects of various organic anions and bile acid conjugates on the biliary excretion of pravastatin in rats.


METHODS
[14C]pravastatin was intravenously injected into rats with bile drainage in the presence and absence of the continuous infusion of organic anions and bile acids, and radioactivity of its biliary excretion was studied.


RESULTS
Biliary excretion of [14C]pravastatin was markedly inhibited by sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, ursodeoxycholate-3, 7-sulfate, and ursodeoxycholate-3-O-glucuronide. In contrast, dibromosulfophthalein only slightly inhibited biliary pravastatin excretion, and cefpiramide did not affect biliary pravastatin excretion.


CONCLUSIONS
These findings further support the multiplicity of canalicular organic anion transport, and pravastatin is considered to be excreted through a canalicular transporter which is absent in EHBR in addition to through cMOAT.
Fukumura
S
S
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Takikawa
H
H
Yamanaka
M
M
D000818:Animals; D027321:Anion Transport Proteins; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics*; D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology*; D001652:Bile Ducts / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000187:drug effects / Q000502:physiology; D005965:Glucuronates / Q000494:pharmacology*; D008297:Male; D017035:Pravastatin / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000494:pharmacology*
D027321:Anion Transport Proteins; D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D005965:Glucuronates; D013431:Sulfates; D017035:Pravastatin