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Drug Transporter Interactions & DDI


  • Drug transporter assays
  • Drug interactions
  • Flux and net transporter measurements
  • Measurement of intracellular drug and metabolite concentrations


  • aProximate™ kidney proximal tubule cells


  • 2-3 months

Investigate renal drug transport modalities and drug interactions in vitro

aProximate™ PTCs retain high expression of the relevant transporters involved in drug handling including megalin and cubilin; so are ideal for drug transporter and drug interaction studies of both small and large molecules. Transporters play a major role in the uptake and efflux of drugs across cellular membranes. Drug interactions with transporter proteins are common and can act either as substrates and/or inhibitors, a role which is best be identified during the early-stages of drug development to define the absorption, distribution, metabolism and excretion (ADME) profile. Using our scientific expertise, Newcells provides transporter assays using the aProximate™ model to support your specific requirements and understand potential drug interactions.

Service outputs

  • Apical to Basal (Jab) and Basal to Apical (Jba) flux
  • Net transport measurements
  • Measurement of intracellular drug and metabolite concentrations
  • Identification of transporter-mediated drug interactions

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A graph of a mate2k drug interactions


Multiple species


Newcells aProximate™ model

Accelerate your lead compound selection by understanding their mode of action in kidney tissue


Fully differentiated and polarised kidney proximal tubule cells


Expression of all relevant renal transporters


High predictivity of in vivo physiology and clinical outcomes

Example 1: In vitro investigation of drug-drug interactions Close Open

The aProximate™ model has been tested for its ability to mimic the renal clearance of the drug probenecid. In vivo renal clearance of probenecid is significantly reduced by the co-administration of other drugs such as para-aminohippurate (PAH), furosemide, cidofovir or fexofenadine, indicating drug-drug interactions via renal transporters, OAT-1 and OAT-3. The aProximate™ model reproduces the interaction between PAH and probenecid observed in vivo. The figure below shows a significant reduction of PAH basolateral to apical flux (JBA) and net flux (JNet) measured in the presence of probenecid in aProximate™ PTCs. This observation demonstrates that aProximate™ recapitulates proximal tubule function and accurately predicts renal drug-drug interactions.

A reliable model to assess drug/drug interactions (DDI). In vivo renal clearance of drugs is reduced by the OAT inhibitor probenecid (upper panel). A similar effect is observed in vitro using the aProximate™ model (bottom panel).
Example 2: Mechanistic insights into drug renal clearance Close Open

Several drugs and metabolites are handled by the same transporters. For example, creatinine, an endogenous metabolite, and the immunomodulating drug pyrimethamine are both substrates for basolateral OCT2 and apical MATE transporters. OATs and MATE transport organic anions, organic compounds like creatinine, but also organic cationic drugs, such as metformin, a common drug used to treat type 2 diabetes.

The excretion of creatinine can be blocked by administering transporter inhibitors such as cimetidine and pyrimethamine. In addition, inhibition of OCT and MATE transporters by cimetidine and pyrimethamine in vivo also reduces metformin renal clearance. Cimetidine interferes with the uptake of metformin by proximal tubule cells and pyrimethamine with efflux of metformin.  In vivo, this leads to a significant increase in systemic exposure and a decrease in metformin renal clearance because metformin and pyrimethamine compete for efflux mediated by MATEs. This data shows that our proximal tubule model enables the investigation of the mechanisms of drug interactions in the kidney.

Predictions of drug/transporter interactions in aProximate™ showing a reduction in renal clearance of metformin upon inhibition of OCT and MATE transporters, comparable to that observed in vivo.
Service Overview Close Open

Our service provides insights into drug interactions:

aProximate™ PTCs have high expression of all key transporters involved in drug absorption, excretion and drug interactions including OAT1 and OCT2 (Brown et al., 2008). We also offer species comparison as aProximate™ PTCs are available from multiple species such as human, rat, dog and NHP.

Substrate assessment and inhibition services using our transporter assay are carried out rapidly to generate data necessary to progress lead compounds into clinical development.

The data generated from our transporter assays has been used for IND submissions by providing comprehensive drug metabolism, transporter and drug interaction data by testing parameters which follows regulatory guidelines.

Our project timelines are short due to our regular supply of fresh kidney tissue. The robust data generated by our scientific experts will guide you in confidence for key decision-making steps during drug development.

An example of transporter drug interaction packages includes assessment of transepithelial flux in proximal tubule cells, specifically Apical to Basal (Jab) and Basal to Apical (Jba) flux, as well as net transport measurements. We can also measure the magnitude of intracellular accumulation across both the apical and basolateral membranes. Data can be derived from three separate biological donor kidneys across multiple species.

Assay design

aProximate™ primary isolated kidney proximal tubule cells

Assay format

24-well Transwell® plates

  • Human
  • Mouse
  • Rat
  • Dog
  • NHP
Assay readout
  • Apical to Basal (Jab) and Basal to Apical (Jba) flux
  • Net transport measurements
  • Measurement of intracellular drug and metabolite concentrations
Time points and replicates
  • 0, 30, 60, 90, 120 minutes
  • Data points are usually performed in triplicates

Models from for this service

aProximate™ proximal tubule cells

aProximate™ is one of the most advanced, near physiological, in vitro kidney proximal tubule cell (PTCs) models. aProximate™ PTCs are derived from fresh human kidney tissue and grown on Transwells® where they remain well differentiated as a polarised cell layer that forms tight junctions.

Find out more
A microscope image of a nephron model
ZO-1 Staining of tight junctions between aProximate™ proximal tubule cells

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