Renal Proximal Tubule Cell Monolayer Assay

Service Cell Line Transporter Technology Membrane Type Probe Substrate Read Out Reference Inhibitor Positive Control Dynamic Range

Description

Kidney Proximal Tubule Cell Monolayer Assay

Renal proximal tubule cell (PTC) monolayer is a unique in vitro approach for investigating renal drug handling, identifying drug-transporter interactions, potential nephrotoxicity and transporter mediated drug-drug interactions. SOLVO offers tailored services in partnership with Newcastle University, UK.

A key deficiency in the drug development process is the availability of applicable preclinical models that can be used to predict toxicological or efficacious outcomes in the clinical setting. Many widely used preclinical models of transport in the kidney are based on transfected human or animal cells which express a limited number of human renal transporters, and so do not accurately reflect the situation in vivo wherein the complex interplay between multiple transporters, determined by their relative protein expression and cellular localization, is key to the process of drug translocation. In contrast, the primary renal proximal tubule cell (PTC) monolayer assay maintains the full complement and expression level of endogenous renal transporters, resulting in a more physiologically relevant, and therefore predictive, model of drug handling and nephrotoxicity in the clinical setting.

The kidney proximal tubular cell monolayer assay is an ideal in vitro platform for:

• Drug safety studies.
• Determination of species differences in the handling of key molecules between rodent and human kidney PTCs to better enable prediction of human toxicity from preclinial animal models.
• Generating in vitro – in vivo correlations for the handling of a wide range of drug molecules with diverse physicochemical properties and renal clearance rates.
• Understanding which transporters at the apical and basolateral membrane of human proximal tubule cells are key in determining the renal handling of a drug molecule, and which therefore may be involved in drug-drug interactions which may result in changes to the pharmacokinetic and toxicokinetic profile of the compound.

The following parameters can be measured on human, rat and mouse PTC models in partnership with Newcastle University:

• Flux measurement, including determination of paracellular contribution to total flux.
• Net transport measurements.
• Measurement of intracellular drug and metabolite concentrations.
• Mechanistic understanding of the role and importance of individual transporters to the renal clearance pathway.
• Identification of potential transporter-mediated drug-drug interactions.
• Investigation of nephrotoxic potential using a panel of early damage biomarkers.

Learn more about Renal Proximal Tubule Cell Monolayer Technology.

Please also download our recently held webinar on this topic!

Title: Predictive cross-species proximal tubule cell models for drug development and safety assessment studies
Presented on February 25th, 2015 by Colin Brown, Ph.D., Associate Professor, Institute for Cell and Molecular Biosciences, Medical School Newcastle University, Newcastle, UK

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