title: Biliary excretion of azelnidipine, a calcium antagonist, in rats.
abstract: 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.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hanawa
authors.forename: Naoyo
authors.initials: N
authors.lastname: Sano
authors.forename: Hajime
authors.initials: H
authors.lastname: Takikawa
mesh_terms: 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
chemical_list: 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