Abstract:
:YM466, a novel factor Xa inhibitor, is a hydrophilic compound with a carboxylic acid moiety. Previous studies in rats have shown that YM466 does nor undergo metabolism but is excreted into the bile and urine in unchanged form. Thus, in this study, we investigated in vivo hepatobiliary transport, focusing in particular on multidrug resistance-associated protein 2 (Mrp2/Abcc2)-mediated transport. The hepatobiliary transport of YM466 was investigated after its systemic infusion into Sprague-Dawley rats (SDRs) and Eisai hyperbilirubinemic rats (EHBRs), which lack Mrp2. When the binding of YM466 in the plasma and liver was examined, the bile-to-plasma concentration ratio and the liver-to-plasma concentration ratio for the unbound concentration in SDRs amounted to 32.2 and 2.83, respectively, suggesting concentrated transport. The bile-to-liver concentration ratio for the unbound concentration in EHBRs was not lower than that found for SDRs. These findings suggest that YM466 is excreted from the plasma into the bile in a concentrated manner; however, Mrp2 does not play a major role in biliary excretion.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Mano Y,Usui T,Kamimura Hdoi
10.1007/BF03191128subject
Has Abstractpub_date
2006-04-01 00:00:00pages
117-21issue
2eissn
0378-7966issn
2107-0180journal_volume
31pub_type
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