Biliary excretion of azelnidipine, a calcium antagonist, in rats.
OBJECTIVE
Azelnidipine (CS-905) is a novel dihydropyridine calcium antagonist that is known to be excreted in feces. To examine the mechanism of biliary excretion of azelnidipine, the authors studied its biliary excretion in Eisai hyperbilirubinuria rats (EHBR), multidrug resistance protein (Mrp)2-deficient rats, and the effect of cholephilic compounds on the biliary excretion of azelnidipine in rats.


METHODS
Radiolabeled azelnidipine was intravenously administered to EHBR and control rats, and the biliary excretion of radiolabeled metabolites was studied. Furthermore, the effect of sulfobromophthalein, taurocholate and vinblastine on the biliary excretion of azelnidipine metabolites was also studied in control rats.


RESULTS
The biliary excretion of azelnidipine metabolites was delayed in EHBR. The biliary excretion of azelnidipine metabolites was inhibited by sulfobromophthalein and vinblastine, but was not inhibited by taurocholate or phenothiazine pretreatment.


CONCLUSIONS
These findings suggest that the metabolites of azelnidipine are excreted into the bile partly by Mrp2 and P-glycoprotein.
Hanawa
Naoko
N
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Sano
Naoyo
N
Takikawa
Hajime
H
D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004095:Dihydropyridines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006932:Hyperbilirubinemia / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000172:deficiency*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000172:deficiency*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013448:Sulfobromophthalein / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
D001383:Azetidinecarboxylic Acid; D002121:Calcium Channel Blockers; D002756:Cholagogues and Choleretics; D004095:Dihydropyridines; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013448:Sulfobromophthalein; D013656:Taurocholic Acid; D014747:Vinblastine; C061679:azelnidipine