کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2568133 1561164 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vitro and in vivo evaluations of the P-glycoprotein-mediated efflux of dibenzoylhydrazines
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
In vitro and in vivo evaluations of the P-glycoprotein-mediated efflux of dibenzoylhydrazines
چکیده انگلیسی


• Transport of DBHs by P-gp was not detected in in vitro bidirectional transport assay.
• DBHs were weak P-gp transport substrates based on in vivo studies in rats.
• The in vivo studies are useful methods for evaluating P-gp transport substrates.
• DBHs inhibit quinidine transport by P-gp in in vitro bidirectional transport assay.

P-glycoprotein (P-gp) is a member of the ATP-binding cassette transporter family. It actively transports a wide variety of compounds out of cells to protect humans from xenobiotics. Thus, determining whether chemicals are substrates and/or inhibitors of P-gp is important in risk assessments of pharmacokinetic interactions among chemicals because P-gp-mediated transport processes play a significant role in their absorption and disposition. We previously reported that dibenzoylhydrazines (DBHs) such as tebufenozide and methoxyfenozide (agrochemicals) stimulated P-gp ATPase activity. However, it currently remains unclear whether these derivatives are transport substrates of P-gp and inhibit transport of other chemicals by P-gp.In the present study, in order to evaluate the interactions of DBHs with other chemicals in humans, we determined whether DBHs are P-gp transport substrates using both the in vitro bidirectional transport assay and the in vivo study of rats. In the in vivo study, we investigated the influence of P-gp inhibitors on the brain to plasma ratio of methoxyfenozide in rats. We also examined the inhibitory effects of DBHs on quinidine (a P-gp substrate) transport by P-gp in order to ascertain whether these derivatives are inhibitors of P-gp. Based on the results, DBHs were concluded to be weak P-gp transport substrates and moderate P-gp inhibitors. However, the risk of DBHs caused by interaction with other chemicals including drugs was considered to be low by considering the DBHs' potential as the substrates and inhibitors of P-gp as well as their plasma concentrations as long as DBHs are properly used.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 298, 1 May 2016, Pages 40–47
نویسندگان
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