In Vitro Methods to Support Transporter Evaluation in Drug Discovery and Development

被引：205

作者：

Brouwer, K. L. R. ^{[1
]}

Keppler, D. ^{[2
]}

Hoffmaster, K. A. ^{[3
]}

Bow, D. A. J. ^{[4
]}

Cheng, Y. ^{[5
]}

Lai, Y. ^{[5
]}

Palm, J. E. ^{[6
]}

Stieger, B. ^{[7
]}

Evers, R. ^{[8
]}

机构：

[1] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27515 USA

[2] German Canc Res Ctr, Heidelberg, Germany

[3] Novartis Inst BioMed Res Metab & Pharmacokinet, Cambridge, MA USA

[4] AbbVie Inc, Dept Drug Metab & Pharmacokinet, N Chicago, IL USA

[5] Bristol Myers Squibb Co, Pharmaceut Candidate Optimizat, Princeton, NJ USA

[6] AstraZeneca R&D, Innovat Med, CVGI iMed DMPK, Molndal, Sweden

[7] Univ Zurich Hosp, Dept Clin Pharmacol & Toxicol, CH-8091 Zurich, Switzerland

[8] Merck & Co Inc, Dept Pharmacokinet Pharmacodynam & Drug Metab, Rahway, NJ 07065 USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2013年 / 94卷 / 01期

基金：

美国国家卫生研究院;

关键词：

BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; GLYCOPROTEIN-MEDIATED TRANSPORT; P-GLYCOPROTEIN; BILIARY-EXCRETION; HEPATIC-UPTAKE; MEMBRANE TRANSPORTERS; EFFLUX TRANSPORTERS; CONFLUENT MONOLAYER; SPECIES-DIFFERENCES; VIVO CORRELATION;

D O I：

10.1038/clpt.2013.81

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

This white paper addresses current approaches and knowledge gaps concerning methods to assess the role of transport proteins in drug/metabolite disposition in humans. The discussion focuses on in vitro tools to address key questions in drug development, including vesicle- and cell-based systems. How these methods can be used to assess the liability of compounds for transporter-based drug-drug interactions (DDIs) in vivo is also explored. Existing challenges and approaches to examine the involvement of transporters in drug disposition are discussed.

引用

页码：95 / 112

页数：18

共 75 条

[1]

In vitro biliary clearance of angiotensin II receptor blockers and 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors in sandwich-cultured rat hepatocytes: Comparison with in vivo biliary clearance [J].

Abe, Koji ;

Bridges, Arlene S. ;

Yue, Wei ;

Brouwer, Kim L. R. .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2008, 326 (03) :983-990

[2]

Use of Sandwich-Cultured Human Hepatocytes to Predict Biliary Clearance of Angiotensin II Receptor Blockers and HMG-CoA Reductase Inhibitors [J].

Abe, Koji ;

Bridges, Arlene S. ;

Brouwer, Kim L. R. .

DRUG METABOLISM AND DISPOSITION, 2009, 37 (03) :447-452

[3]

Kinetic identification of membrane transporters that assist P-glycoprotein-mediated transport of digoxin and loperamide through a confluent monolayer of MDCKII-hMDR1 cells [J].

Acharya, Poulomi ;

O'Connor, Michael P. ;

Polli, Joseph W. ;

Ayrton, Andrew ;

Ellens, Harma ;

Bentz, Joe .

DRUG METABOLISM AND DISPOSITION, 2008, 36 (02) :452-460

[4]

Endogenous Gene and Protein Expression of Drug-Transporting Proteins in Cell Lines Routinely Used in Drug Discovery Programs [J].

Ahlin, Gustav ;

Hilgendorf, Constanze ;

Karlsson, Johan ;

Szigyarto, Cristina Al-Khalili ;

Uhlen, Mathias ;

Artursson, Per .

DRUG METABOLISM AND DISPOSITION, 2009, 37 (12) :2275-2283

[5]

Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions [J].

Bakos, É ;

Evers, R ;

Sinkó, E ;

Váradi, A ;

Borst, P ;

Sarkadi, B .

MOLECULAR PHARMACOLOGY, 2000, 57 (04) :760-768

[6]

Data-based mathematical Modeling of vectorial transport across double-transfected polarized cells [J].

Bartholome, Kilian ;

Rius, Maria ;

Letschert, Katrin ;

Keller, Daniela ;

Timmer, Jens ;

Keppler, Dietrich .

DRUG METABOLISM AND DISPOSITION, 2007, 35 (09) :1476-1481

[7]

The role of BCS (biopharmaceutics classification system) and BDDCS (biopharmaceutics drug disposition classification system) in drug development [J].

Benet, Leslie Z. .

JOURNAL OF PHARMACEUTICAL SCIENCES, 2013, 102 (01) :34-42

[8]

In Vitro Evaluation of Hepatic Transporter-Mediated Clinical Drug-Drug Interactions: Hepatocyte Model Optimization and Retrospective Investigation [J].

Bi, Yi-an ;

Kimoto, Emi ;

Sevidal, Samantha ;

Jones, Hannah M. ;

Barton, Hugh A. ;

Kempshall, Sarah ;

Whalen, Kevin M. ;

Zhang, Hui ;

Ji, Chengjie ;

Fenner, Katherine S. ;

El-Kattan, Ayman F. ;

Lai, Yurong .

DRUG METABOLISM AND DISPOSITION, 2012, 40 (06) :1085-1092

[9]

The conduct of in vitro and in vivo drug-drug interaction studies: A Pharmaceutical Research and Manufacturers of America (PhRMA) perspective [J].

Bjornsson, TD ;

Callaghan, JT ;

Einolf, HJ ;

Fischer, V ;

Gan, L ;

Grimm, S ;

Kao, J ;

King, SP ;

Miwa, G ;

Ni, L ;

Kumar, G ;

McLeod, J ;

Obach, RS ;

Roberts, S ;

Roe, A ;

Shah, A ;

Snikeris, F ;

Sullivan, JT ;

Tweedie, D ;

Vega, JM ;

Walsh, J ;

Wrighton, SA .

DRUG METABOLISM AND DISPOSITION, 2003, 31 (07) :815-832

[10]

BOHME M, 1994, GASTROENTEROLOGY, V107, P255

← 1 2 3 4 5 6 7 8 →