fitting the elementary rate constants of the p-gp transporter network in the hmdr1-mdck confluent cell monolayer using a particle swarm algorithm拟合的基本速率常数p-gp运输网络hmdr1-mdck汇合的细胞单层使用粒子群算法.pdfVIP

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fitting the elementary rate constants of the p-gp transporter network in the hmdr1-mdck confluent cell monolayer using a particle swarm algorithm拟合的基本速率常数p-gp运输网络hmdr1-mdck汇合的细胞单层使用粒子群算法.pdf

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fitting the elementary rate constants of the p-gp transporter network in the hmdr1-mdck confluent cell monolayer using a particle swarm algorithm拟合的基本速率常数p-gp运输网络hmdr1-mdck汇合的细胞单层使用粒子群算法

Fitting the Elementary Rate Constants of the P-gp Transporter Network in the hMDR1-MDCK Confluent Cell Monolayer Using a Particle Swarm Algorithm 1¤a 1¤b 1 2 3¤c Deep Agnani , Poulomi Acharya , Esteban Martinez , Thuy Thanh Tran , Feby Abraham , Frank 3¤d 2 1 Tobin , Harma Ellens , Joe Bentz * 1 Department of Biology, Drexel University, Philadelphia, Pennsylvania, United States of America, 2 Preclinical Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America, 3 Scientific Computing and Mathematical Modeling, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America Abstract P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp’s transport and to functionally characterize members of P-gp’s network, i.e., other transporters that transport P-gp substrates in hMDR1- MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical s