التفاصيل البيبلوغرافية
العنوان:
A Comprehensive Study Demonstrating that P-glycoprotein Function is Directly Affected by Changes in pH: Implications for Intestinal pH and Effects on Drug Absorption
المؤلفون:
Kenneth L. Audus , Gervan Williams , Deborah Galinis , Mehran Yazdanian , Pallabi Mitra
المصدر:
Journal of Pharmaceutical Sciences . 100:4258-4268
بيانات النشر:
Elsevier BV, 2011.
سنة النشر:
2011
مصطلحات موضوعية:
Digoxin , ATP Binding Cassette Transporter, Subfamily B , Protein Conformation , Biological Availability , Pharmaceutical Science , Pharmacology , Transfection , Permeability , Intestinal absorption , Madin Darby Canine Kidney Cells , Structure-Activity Relationship , chemistry.chemical_compound , Adenosine Triphosphate , Dogs , Extracellular , Animals , Humans , Colchicine , Intestinal Mucosa , P-glycoprotein , biology , Chemistry , Hydrolysis , Biological Transport , Hydrogen-Ion Concentration , Bioavailability , Intestinal Absorption , Caco-2 , Permeability (electromagnetism) , biology.protein , Efflux , Caco-2 Cells
الوصف:
The purpose of this study was to investigate whether changes in the pH of the gastrointestinal tract can directly affect P-glycoprotein (P-gp) function. The effect of changes in extracellular pH on P-gp functionality was examined by testing colchicine (a nonionizable P-gp substrate) in bidirectional Caco-2 and MDR1–Madine Darby canine kidney (MDCK) cell permeability assays, in which the pH of the apical and basolateral chambers was varied. Reduction of the pH from 7.4 to 5.0 and 4.5 markedly increased the apical-to-basolateral flux of colchicine and reduced the basolateral-to-apical flux. The efflux ratio for colchicine was reduced to 1.2 at pH 4.5, compared with values greater than 20 that were measured in the pH range of 5.5–7.4. A similar result was obtained when MDR1–MDCK cells were used in the bidirectional permeability studies. Other nonionizable P-gp substrates (digoxin, dexamethasone, paclitaxel, and etoposide) responded to acidic pH (4.5) in a manner similar to colchicine. Reduced P-gp ATPase activity is a reason for the diminished P-gp function observed at pH 4.5. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4258–4268, 2011
تدمد:
0022-3549
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::258eedc15ae765151a6c73707c0c6b31 https://doi.org/10.1002/jps.22596
حقوق:
CLOSED
رقم الأكسشن:
edsair.doi.dedup.....258eedc15ae765151a6c73707c0c6b31
قاعدة البيانات:
OpenAIRE
