药品
抗药性
流出
P-糖蛋白
阿霉素
运输机
化学
作者
Robert Elsby,Veronica Smith,Lisa Fox,David M. Stresser,Caroline Butters,Pradeep Sharma,Dominic Surry
出处
期刊:Xenobiotica
[Informa]
日期:2011-08-03
卷期号:41 (9): 764-783
被引量:26
标识
DOI:10.3109/00498254.2011.578761
摘要
Breast cancer resistance protein (BCRP) and multidrug resistance protein 2 (MRP2) can play a role in the absorption, distribution, metabolism, and excretion of drugs, impacting on the potential for drug–drug interactions. This study has characterized insect cell– and mammalian cell–derived ABC-transporter–expressing membrane vesicle test systems and validated methodologies for evaluation of candidate drugs as substrates or inhibitors of BCRP or MRP2.Concentration-dependent uptake of BCRP ([3H]oestrone 3-sulfate, [3H]methotrexate, [3H]rosuvastatin) and MRP2 ([3H]oestradiol 17β-glucuronide, [3H]pravastatin, carboxydichlorofluorescein) substrates, and inhibitory potencies (IC50) of BCRP (sulfasalazine, novobiocin, fumitremorgin C) and MRP2 (benzbromarone, MK-571, terfenadine) inhibitors were determined.The apparent Km for probes [3H]oestrone 3-sulfate and [3H]oestradiol 17β-glucuronide was determined in insect cell vesicles to be 7.4 ± 1.7 and 105 ± 8.3 µM, respectively. All other substrates exhibited signif...
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