Solute carrier transporter and drug-related nephrotoxicity: the impact of proximal tubule cell models for preclinical research

Abstract

Introduction: The final excretion step of several drugs is facilitated by membrane transporters of the Solute carrier (SLC) family expressed in the proximal tubules of the kidney. Membrane transporters contribute substantially to the pharmacokinetic profile of drugs and play important roles in drug-induced nephrotoxicity. Different cell models have been applied as tools for the assessment of nephrotoxic effects caused by drugs.

Areas covered: This review gives an overview over clinically relevant SLC transporters involved in the renal elimination of drug agents and their specific role in drug-induced nephrotoxicity. Most widely applied cell models are described and their advantages and limitations are outlined.

Expert opinion: In vitro cell culture models (e.g., continuous and primary renal cell lines, polarized cell monolayers) represent valuable tools for early assessment of the nephrotoxic potential of drugs. Since SLC transporters contribute to drug excretion in a large part, in vitro cell culture models might be very helpful to study transport pathways and/or potential drug–drug interactions at an early stage of the drug development process to predict nephrotoxic effects.

Keywords::

• drug–drug interaction
• drug-induced nephrotoxicity
• in vitro cell models
• organic anion/cation transporters
• pharmacogenomics
• SLC transporter

Notes

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