کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484293 | 1114305 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Usefulness of A Model-Based Approach for Estimating In Vitro P-Glycoprotein Inhibition Potency in a Transcellular Transport Assay
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کلمات کلیدی
P-glycoprotein - P-گلیکوپروتئینInhibition - بازداریDrug interactions - تداخل داروییTransporters - حمل و نقلmembrane transport/transporters - حمل و نقل غشاء / حمل و نقلABC transporters - حمل کننده ABCCaco-2 cells - سلول های Caco-2Pharmacokinetics - فارماکوکینتیکMathematical models - مدل ریاضیEfflux pumps - پمپ های خروجی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Usefulness of A Model-Based Approach for Estimating In Vitro P-Glycoprotein Inhibition Potency in a Transcellular Transport Assay Usefulness of A Model-Based Approach for Estimating In Vitro P-Glycoprotein Inhibition Potency in a Transcellular Transport Assay](/preview/png/2484293.png)
چکیده انگلیسی
In vitro half-maximal inhibitory concentration (IC50) is a key parameter for accurately predicting the potential risk for P-glycoprotein (P-gp)-mediated drug-drug interactions. We aimed to compare the IC50 values estimated by different approaches and determine the usefulness of model-based approaches. Transcellular transport of digoxin across Caco-2 monolayer was investigated using various concentrations of P-gp inhibitors, quinidine, verapamil, and zosuquidar. To calculate IC50 values, 3 traditional parameters were used: apical-to-basal (AtoB) and basal-to-apical (BtoA) clearance (CL) with inhibitors (CLAtoB,i and CLBtoA,i) and the difference between the efflux ratios (ERs) with P-gp inhibitors (ERi) and those under complete P-gp inhibition [ER(âP-gp)]. Furthermore, a new model-based approach was applied that uses the difference between the reciprocals of CLAtoB with P-gp inhibitors (1/CLAtoB,i) and those under complete P-gp inhibition [1/CLAtoB(âP-gp)] as parameters. IC50 values obtained from 2 model-based approaches [ERi â ER(âP-gp) and 1/CLAtoB,i â 1/CLAtoB(âP-gp)] were comparable, whereas 2.6- to 6.6-fold larger IC50 values were estimated from empirical approaches (CLAtoB,i and CLBtoA,i). The reason for such difference in IC50 values is that indicators for model-based approaches, but not empirical approaches, directly reflect the P-gp function. Our new approach [1/CLAtoB,i â 1/CLAtoB(âP-gp)] based on only AtoB transcellular transport could substitute for current estimation methods using ER.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 2, February 2016, Pages 891-896
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 2, February 2016, Pages 891-896
نویسندگان
Wataru Kishimoto, Naoki Ishiguro, Eva Ludwig-Schwellinger, Thomas Ebner, Kazuya Maeda, Yuichi Sugiyama,