DMD Noab BioDiscoveries - Shaping Drug Discovery

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


     

Drug Metabolism and Disposition Fast Forward
First published on September 4, 2007; DOI: 10.1124/dmd.107.018044

0090-9556/07/3512-2154-2158$20.00
DMD 35:2154-2158, 2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.107.018044v1
35/12/2154    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 Zhang, Y.
Right arrow Articles by Mao, Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, Y.
Right arrow Articles by Mao, Q.

Breast Cancer Resistance Protein 1 Limits Fetal Distribution of Nitrofurantoin in the Pregnant Mouse

Yi Zhang, Honggang Wang, Jashvant D. Unadkat, and Qingcheng Mao

Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington

The efflux transporter, the breast cancer resistance protein (BCRP), is most abundantly expressed in the apical membrane of the placental syncytiotrophoblasts, indicating that it could play an important role in protecting the fetus by limiting xenobiotic/drug penetration across the placental barrier. In the present study, we examined whether Bcrp1, the murine homolog of human BCRP, limits fetal distribution of the model BCRP/Bcrp1 substrate, nitrofurantoin (NFT), in the pregnant mouse. NFT was administered i.v. to FVB wild-type and Bcrp1–/– pregnant mice. The maternal plasma samples and fetuses were collected at various times (5–60 min) after drug administration. The NFT concentrations in the maternal plasma samples and homogenates of fetal tissues were determined by a high-performance liquid chromatography/UV assay. Although the maternal plasma area under the concentration-time curve (AUC) of NFT in the Bcrp1–/– pregnant mice (97.4 ± 10.0 µg · min/ml plasma) was only slightly (but significantly) higher than that in the wild-type pregnant mice (78.4 ± 6.0 µg · min/ml plasma), the fetal AUC of NFT in the Bcrp1–/– pregnant mice (1493.0 ± 235.3 ng · min/g of fetus) was approximately 5 times greater than that in the wild-type pregnant mice (298.6 ± 77.4 ng · min/g of fetus). These results clearly suggest that Bcrp1 significantly limits fetal distribution of NFT in the pregnant mouse, but has only a minor effect on the systemic clearance of the drug.

Address correspondence to: Dr. Qingcheng Mao, Department of Pharmaceutics, School of Pharmacy, Box 357610, University of Washington, Seattle, WA 98195. E-mail: qmao{at}u.washington.edu




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
L. M. Aleksunes, Y. Cui, and C. D. Klaassen
Prominent Expression of Xenobiotic Efflux Transporters in Mouse Extraembryonic Fetal Membranes Compared with Placenta
Drug Metab. Dispos., September 1, 2008; 36(9): 1960 - 1970.
[Abstract] [Full Text] [PDF]


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

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics.