DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on November 8, 2006; DOI: 10.1124/dmd.106.012567

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.106.012567v1
35/2/209    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Enokizono, J.
Right arrow Articles by Sugiyama, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Enokizono, J.
Right arrow Articles by Sugiyama, Y.


Received for publication August 28, 2006.
Revised November 1, 2006.
Accepted for publication November 1, 2006.

Involvement of Breast Cancer Resistance Protein (BCRP/ABCG2) in the biliary excretion and intestinal efflux of troglitazone sulfate, the major metabolite of troglitazone with a cholestatic effect

Junichi Enokizono 1, Hiroyuki Kusuhara 1, Yuichi Sugiyama 1*

1 The University of Tokyo

* Address correspondence to: E-mail: sugiyama{at}mol.f.u-tokyo.ac.jp

Abstract

Troglitazone sulfate (TGZS) is the major metabolite of troglitazone, an anti-diabetic agent, and thought to be a cause of the cholestasis induced by troglitazone (TGZ). The aim of the present study is to elucidate the involvement of breast cancer resistance protein (BCRP/ABCG2) in the hepatic disposition of TGZS. The basal-to-apical transport of TGZS was enhanced in OATP1B1 expressing MDCK II cells by infection of recombinant adenovirus harbouring hBCRP and mBcrp cDNA. TGZS was given to wild-type and Bcrp (-/-) mice by constant infusion. Biliary excretion is the predominant elimination pathway of TGZS in wild-type mice, and the biliary excretion clearance of TGZS with regard to the hepatic concentration was reduced to 30% of the control in Bcrp (-/-) mice. However, plasma and hepatic concentrations were unchanged, suggesting induction of compensatory mechanisms in Bcrp (-/-) mice for the elimination of TGZS. Involvement of BCRP in the intestinal efflux transport of TGZS was examined using everted sacs. The mucosal efflux clearance of TGZS showed only a slight reduction (15% reduction) in Bcrp (-/-) mice. Our results suggest that BCRP plays a major role in the biliary excretion, but a minor role in the intestinal transport of TGZS.


Key words: ABC transporters, absorption, drug efflux, drug transport, hepatic elimination, hepatic transport, hepatobiliary disposition, hepatobiliary transport, transporters


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
J. Enokizono, H. Kusuhara, A. Ose, A. H. Schinkel, and Y. Sugiyama
Quantitative Investigation of the Role of Breast Cancer Resistance Protein (Bcrp/Abcg2) in Limiting Brain and Testis Penetration of Xenobiotic Compounds
Drug Metab. Dispos., June 1, 2008; 36(6): 995 - 1002.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
J. Enokizono, H. Kusuhara, and Y. Sugiyama
Regional Expression and Activity of Breast Cancer Resistance Protein (Bcrp/Abcg2) in Mouse Intestine: Overlapping Distribution with Sulfotransferases
Drug Metab. Dispos., June 1, 2007; 35(6): 922 - 928.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2006 by the American Society for Pharmacology and Experimental Therapeutics.