Drug Transporter (e.g. P-gp) Substrate Potential

We offer definitive in vitro transporter studies to determine if a drug compound may be a victim (substrate) in transporter-mediated drug-drug interactions (DDI) using validated, industry-accepted test systems for major drug transporters including P-gp, BCR, and others, in compliance with regulatory guidance.

The intention of DDI studies in a preclinical data package is to prevent patients’ unnecessary exclusion from clinical trial participation by predicting potential for harmful interactions with concomitant drugs through a risk-based approach. Part of necessary investigations into DDI potential of a compound focuses on proteins involved in transporting compounds across membranes. Clinically-relevant drug transporters can be found in various tissues such as the intestine, liver, kidney, and brain and can have a significant impact on a drug’s disposition and pharmacokinetics.

Our Approach to Evaluating Drug Transporter Substrate Potential

To address direction from the Food and Drug Administration (FDA) to “determine if the investigational drug is a substrate of a transporter” (In Vitro Drug Interactions Studies— Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions: Final Guidance for Industry, FDA 2020), we offer studies designed to evaluate a compound’s substrate (victim) potential with appropriate transporters in studies designed to meet current FDA, European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA) expectations for new drug applications.

P-gp & others: FDA-specified transporters for standard investigation of substrate potential of a compound

ABC/efflux: P-gp and BCRP substrate potential recommended (except for highly-soluble, highly-permeable drugs)
SLC/uptake: Hepatic (OAT1B1, OATP1B3) and renal (OAT1, OAT3, OCT2, MATE1, MATE2-K) substrate potential should be evaluated based on ADME (absorption, distribution, metabolism, excretion) data if it suggests hepatic uptake/elimination or renal secretion is significant.

P-gp substrate potential studies explore interaction between a compound and drug transporters

In Vitro Substrate Potential Assays We Offer

Test systems and study design are determined by whether the drug transporter is associated with efflux or uptake.

P-gp and BCRP are common efflux (ABC) transporters, and uptake (SLC) transporters include OATs and MATEs. Find more information by transporter type:

SLC (Uptake) Transporter Assays – Substrate & Inhibition

Uptake Transporter substrate potential is measured by comparing the accumulation of the test compound in renal and hepatic transporter-expressing cells versus control cells.

ABC (Efflux) Transporter Assays (BCRP, P-gp) Substrate & Inhibition

Efflux Transporter (BCRP, P-gp) substrate potential assays measure the bidirectional permeability of the test compound across a monolayer of cells (MDCKII-MDR1 or MDCKII-BCRP) in a transwell plate.

Drug Transport-Related Scientific Content

For more information to guide your decision making on timing and individual transporters (such as P-gp and BCRP) to assess, discover our Drug Transporters Decision Tree, a poster comparing of regulatory expectations between FDA, EMA, and PMDA or our extensive collection of transporter-related scientific content.

Additional features of our drug transport study design and a chart of known clinically relevant transporter DDIs can be found on our Drug Transport Services page.

Related Services: Transporter Inhibition Screening

Discovery Plus™ Screening Suite presents medium-throughput alternatives to definitive metabolism & DDI studies through non-GLP, abbreviated versions of our definitive assays. This option is best used for comparison of multiple compounds or to yield preliminary data for definitive in vitro studies.