کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487624 | 1114424 | 2007 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Interactions of azole antifungal agents with the human breast cancer resistance protein (BCRP)
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
Breast cancer resistance protein (BCRP) is an efflux transporter that plays an important role in drug disposition. The goal of this study was to investigate the interactions of azole antifungal agents, ketoconazole, itraconazole, fluconazole, and voriconazole, with BCRP. First, the effect of the azoles on BCRP efflux activity in BCRPâoverexpressing HEK cells was determined by measuring intracellular pheophorbide A (PhA) fluorescence using flow cytometry. We found that keotoconazole and itraconazole significantly inhibited BCRPâmediated efflux of PhA at low µM concentrations. However, fluconazole only mildly inhibited and voriconazole did not inhibit BCRP efflux activity at concentrations up to 100 µM. The IC50 value of ketoconazole for inhibition of BCRPâmediated PhA efflux was 15.3 ± 6.5 µM. Ketoconazole and itraconazole also effectively reversed BCRPâmediated resistance of HEK cells to topotecan. When direct efflux of [3H]ketoconazole was measured in BCRPâoverexpressing HEK cells, we found that [3H]ketoconazole was not transported by BCRP. Consistent with this finding, BCRP did not confer resistance to ketoconazole and itraconazole in HEK cells. Taken together, ketoconazole and itraconazole are BCRP inhibitors, but fluconazole and voriconazole are not. These results suggest that BCRP could play a significant role in the pharmacokinetic interactions of ketoconazole or itraconazole with BCRP substrate drugs. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3226-3235, 2007
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 12, December 2007, Pages 3226-3235
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 12, December 2007, Pages 3226-3235
نویسندگان
Anshul Gupta, Jashvant D. Unadkat, Qingcheng Mao,