Author : Alex D. Morgan
Publisher :
ISBN 13 :
Total Pages : 262 pages
Book Rating : 4.:/5 (16 download)
Book Synopsis Quantitative Estimation of P-glycorptein-mediated Drug Transport by Mechanistically Modeled Intrinsic Clearance by : Alex D. Morgan
Download or read book Quantitative Estimation of P-glycorptein-mediated Drug Transport by Mechanistically Modeled Intrinsic Clearance written by Alex D. Morgan and published by . This book was released on 2015 with total page 262 pages. Available in PDF, EPUB and Kindle. Book excerpt: P-glycoprotein (P-gp/ ABCB1) is an important efflux drug transporter affecting the disposition of 50% of marketed drugs. Cell monolayer permeability assays are the gold sta ndard for assessing P-gp-drug interactions in vitro, but inter-laboratory assay differences produce heterogeneous results. We compared the validity and sensitivity of traditional assay metrics of efflux transport (unidirectional apparent permeability and efflux ratio) wi th a modeled clearance metric, CL P-gp and hypothesized that CL P-gp would be superior. Cell monolayers heterologously transfected with ABCB1, and 1,25(OH) 2 D 3 -modulated ABCB1 in cells served as experimental models. P-gp expression was quantified by western blot and bidir ectional [3 H]-digoxin transcellular flux was measured. Linear regression analys es were performed for P-gp expression versus each P-gp activity metric. The validity and sensitivi ty of modeled clearance was comparable to traditional metrics within a cell type, but wa s superior across different cell types. In conclusion, CL P-gp offers a physiologically-relevant and universally acceptable metric for efflux transport activity.