Journal article
5,7-Dimethoxyflavone and Multiple Flavonoids in Combination Alter the ABCG2-Mediated Tissue Distribution of Mitoxantrone in Mice
Pharmaceutical research, Vol.28(5), pp.1090-1099
2011
DOI: 10.1007/s11095-011-0368-y
PMID: 21279423
Abstract
Purpose
The objective of our study was to investigate the effect of 5,7-DMF on the accumulation of mitoxantrone (MX) in BCRP-expressing normal cells and to investigate its impact on the PK and tissue distribution of MX in mice.
Methods
The in vitro effect of 5,7-DMF on MX accumulation was examined in MDCK cells transfected with BCRP. The pharmacokinetic and tissue distribution of mitoxantrone, with and without co-administration of 5,7-DMF or multiple flavonoid combinations, were determined in mice.
Results
In the presence of 2.5 μM or 25 μM of 5,7-DMF, the intracellular concentration of MX was significantly increased in MDCK/Bcrp1 and MDCK/BCRP cells, but not in MDCK/Mock cells. The AUC values of MX in several tissues were significantly increased when MX was co-administered with 5,7-DMF. The most substantial elevations of MX AUC in the presence of 5,7-DMF occurred in the liver (94.5%) and kidneys (61.9%), which is in apparent agreement with the relatively high levels of mouse Bcrp1 expression in these two tissues.
Conclusions
Bcrp1-mediated DMF-MX interactions occur both in vitro and in vivo. 5,7-DMF represents a novel and very promising chemosensitizing agent for the BCRP-mediated MDR due to its low toxicity and potent BCRP inhibition.
Details
- Title: Subtitle
- 5,7-Dimethoxyflavone and Multiple Flavonoids in Combination Alter the ABCG2-Mediated Tissue Distribution of Mitoxantrone in Mice
- Creators
- Guohua An - Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences University at Buffalo, State University of New York 5 17 Hochstetter Hall, Amherst, New York 14260-1200, United StatesFang Wu - Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences University at Buffalo, State University of New York 5 17 Hochstetter Hall, Amherst, New York 14260-1200, United StatesMarilyn E MORRIS - Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences University at Buffalo, State University of New York 5 17 Hochstetter Hall, Amherst, New York 14260-1200, United States
- Resource Type
- Journal article
- Publication Details
- Pharmaceutical research, Vol.28(5), pp.1090-1099
- Publisher
- Springer; New York, NY
- DOI
- 10.1007/s11095-011-0368-y
- PMID
- 21279423
- ISSN
- 0724-8741
- eISSN
- 1573-904X
- Language
- English
- Date published
- 2011
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065309302771
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