caa a22 4500 445313803 CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11095-011-0368-y doi (NATIONALLICENCE)springer-10.1007/s11095-011-0368-y 5,7-Dimethoxyflavone and Multiple Flavonoids in Combination Alter the ABCG2-Mediated Tissue Distribution of Mitoxantrone in Mice [Elektronische Daten] [Guohua An, Fang Wu, Marilyn Morris] 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 2.5μM or 25μM 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. Springer Science+Business Media, LLC, 2011 BCRP-based drug interaction nationallicence in-vitro / in-vivo correlation nationallicence mitoxantrone nationallicence tissue distribution nationallicence 5,7-dimethoxyflavone nationallicence ABC : ATP binding cassette nationallicence BCRP : breast cancer resistance protein nationallicence DMF : 5,7-dimethoxyflavone nationallicence FTC : fumitremogin C nationallicence I.S : internal standard nationallicence MDCK : Madin-Darby canine kidney nationallicence MDR : multidrug resistance nationallicence MX : mitoxantrone nationallicence PK : pharmacokinetics nationallicence An Guohua Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 517 Hochstetter Hall, 14260-1200, Amherst, New York, USA aut Wu Fang Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 517 Hochstetter Hall, 14260-1200, Amherst, New York, USA aut Morris Marilyn Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 517 Hochstetter Hall, 14260-1200, Amherst, New York, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1090-1099 0724-8741 28:5<1090 2011 28 11095 https://doi.org/10.1007/s11095-011-0368-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0368-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- An Guohua Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 517 Hochstetter Hall, 14260-1200, Amherst, New York, USA aut NATIONALLICENCE 700 1- Wu Fang Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 517 Hochstetter Hall, 14260-1200, Amherst, New York, USA aut NATIONALLICENCE 700 1- Morris Marilyn Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 517 Hochstetter Hall, 14260-1200, Amherst, New York, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1090-1099 0724-8741 28:5<1090 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer