کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8513430 | 1556494 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cellular Pharmacokinetic Model-Based Analysis of Genistein, Glyceollin, and MK-571 Effects on 5 (and 6)-Carboxy-2â²,7â²-Dichloroflourescein Disposition in Caco-2 Cells
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کلمات کلیدی
CDFABCC3CDFDAbasolateral-to-apicalABCC2apical-to-basolateralMRPBcrpclearance - ترخیص کالا از گمرکintestinal secretion/transport - ترشح روده / حمل و نقلMembrane transport - حمل غشاءDrug transport - حمل مواد مخدرTransporters - حمل و نقلTranscellular transport - حمل و نقل بین المللیActive transport - حمل و نقل فعالCaco-2 cells - سلول های Caco-2Pharmacokinetics - فارماکوکینتیکmultidrug resistance-associated protein - پروتئین مرتبط با مقاومت چند داروییbreast cancer resistance protein - پروتئین مقاومت به سرطان سینهEfflux pumps - پمپ های خروجی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Pharmacokinetic modeling was used to describe 5 (and 6)-carboxy-2â²,7â²-dichloroflourescein (CDF) disposition in Caco-2 cells following CDF or CDFDA (CDF diacetate) dosing. CDF transcellular flux was modeled by simple passive diffusion. CDFDA dosing models were based on simultaneous fitting of CDF levels in apical, basolateral, and intracellular compartments. Predicted CDF efflux was 50% higher across the apical versus the basolateral membrane. This difference was similar following apical and basolateral CDFDA dosing, despite intracellular levels being 3-fold higher following basolateral dosing, thus supporting nonsaturable CDF efflux kinetics. A 3-compartment catenary model with intracellular CDFDA hydrolysis described CDF disposition. This model predicted that apical CDF efflux was not altered in the presence of MK-571, and that basolateral membrane clearance was enhanced to account for reduced intracellular CDF in the presence of this multidrug resistance-associated protein (MRP) inhibitor. Similar effects were predicted for glyceollin, while genistein exposure had no predicted effects on CDF efflux. These modulator effects are discussed in the context of model predicted intracellular CDF concentrations relative to reports of CDF affinity (measured by Km) for MRP2 and MRP3. This model-based analysis confirms the complexity of efflux kinetics and suggests that other transporters may have contributed to CDF efflux.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 107, Issue 4, April 2018, Pages 1194-1203
Journal: Journal of Pharmaceutical Sciences - Volume 107, Issue 4, April 2018, Pages 1194-1203
نویسندگان
Callie Drennen, Erin Gorse, Robert E. Jr.,