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Analysis of Renal Transporters

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Transporters in Drug Development

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 7))

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Abstract

The rapid technological advances in the drug transporter field have also greatly enhanced our knowledge on the expression, localization, function, and genetic variation of renal transporters. It is now widely acknowledged that carrier-mediated transport processes in the kidney proximal tubule are an important determinant of drug disposition and the extent to which drugs are accumulated in renal tissue. The study of renal transport has traditionally benefited a lot from physiological studies in isolated membrane vesicles, tubules, tissue slices, perfused kidneys, and intact animals. Together with molecular cloning and over-expression systems we now have a fairly good picture of the individual characteristics of the most important renal transporters. The next challenge will be to reconstruct the complexity of the interplay between the various uptake and efflux transporters of the proximal tubule in experimental and in silico models, in order to accurately predict renal drug clearance, drug–drug interactions, and the risk of nephrotoxicity in different populations. This chapter will give a critical review of current methods available for the exploration of renal drug transport.

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Abbreviations

ABC:

ATP-binding cassette

BBM:

Brush border membrane

BLM:

Basolateral membrane

CHO:

Chinese hamster ovary cell line

ciPTEC:

Human conditionally immortalized proximal tubule epithelial cell line

COS-7:

African green monkey cells

HEK293:

Human embryonic kidney cells

HK-2:

Human immortalized proximal tubule epithelial cell line

LLC_PK1:

Pig kidney epithelial cells

MDCK:

Madin-Darby canine kidney cells

PAH:

para-Amino hippuric acid

pMEG:

9-(2-phosphonylmethoxyethyl)guanine

Sf9:

Spodeptera frugiperda (moth)

SLC:

Solute carrier

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands

    Frans G. M. Russel & Rosalinde Masereeuw

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  1. Frans G. M. Russel
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  2. Rosalinde Masereeuw
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Correspondence to Frans G. M. Russel .

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Editors and Affiliations

  1. The University of Tokyo Graduate School of Pharmac. Sciences, Tokyo, Japan

    Yuichi Sugiyama

  2. Pharma, Drug Transporters in ADME Department of Pharmacy, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark

    Bente Steffansen

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Russel, F.G.M., Masereeuw, R. (2013). Analysis of Renal Transporters. In: Sugiyama, Y., Steffansen, B. (eds) Transporters in Drug Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8229-1_10

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