Drug Transporter Testing Services

Transporters are membrane-bound proteins that enable movement of substances, from nutrients to xenobiotics, in and out of cells. Drug transporter interactions are an important part of the pharmocokinetic properties of drug products. Understanding which transporters drive influx/efflux of your drug can help predict in vivo safety and performance, optimise development, and speed up regulatory approval.

drug transporter illustration

Drug transporters are grouped into two classes:

  • ABC (ATP binding cassette) transporters are relevant for intestinal absorption, urinary excretion and blood-brain barrier transfer. Examples include P-glycoprotein (P-gp) and BCRP.
  • SLC (solute carrier) transporters mainly impact renal and hepatic uptake of drugs, as well as urinary excretion. Examples include OATP1B1 and OCT1.

Our suite of in vitro assays enable robust and comprehensive characterisation of drug interactions with both ABC and SLC transporters. The cell lines and inhibitors we use align with all FDA recommendations for these assays. Find out more about the latest guidance on drug transporter studies here.

 

The Absorption Systems Difference

Absorption Systems has extensive experience evaluating the potential interactions of compounds with drug transporter proteins. We have years of experience with in vitro transporter substrate and inhibitor potential assay development.  Our expertise spans co-medications, product profiles, development plans, clearance routes, chemical structures, and physicochemical properties.

Frequently Asked Questions

Why evaluate the substrate and inhibitor potential of investigational drugs for specific transporters and why do the FDA and EMA care?

Membrane transporters can have clinically relevant effects on the pharmacokinetics and pharmacodynamics of a drug in various organs and tissues by controlling its absorption, distribution, and elimination. Transporter-mediated uptake or efflux of drugs and endogenous compounds may impact the efficacy and safety of the investigational drug and potential concomitant medications. Several key transporters have the potential to interact with drugs in clinical use and the FDA recommends determining if the investigational drug is a substrate and/or an inhibitor of those key transporters.

Why use in vitro assays?

In vitro studies are part of an integrated approach to reduce unnecessary clinical studies. Negative in vitro results can preclude the need for clinical drug-drug interaction (DDI) studies; in some cases it is also possible to waive clinical studies for compounds that do interact with P-gp and/or BCRP. If clinical DDI studies are required, then in vitro results may serve as the basis for design of those studies. Similarly, the results of clinical DDI studies help to explain and refine predictive in vitro models or tools.

Timing of in vitro evaluation

Because it is recommended to evaluate all investigational drugs as inhibitors of P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1 and MATE2-K, and as substrates of P-gp and BCRP, it is suggested to investigate these transporters relatively early in drug development. Furthermore, knowing if the investigational drug is a potential substrate or inhibitor of one of these transporters can help with potential clinical studies down the road.

Are Absorption Systems’ assays validated?

Great results begin with reliable test systems. Your studies are performed in validated test systems supported by our experienced staff who offer regulatory-focused guidance from the initial consultation through final submission. 

OUR CAPABILITIES

Transporter Categories

CellPort Test Systems

Great results begin with reliable test systems, which is why we developed CellPort AnalyticsTM Drug Transporter cell lines. Your studies are performed in validated test systems, supported by our experienced staff who offer regulatory-focused guidance from the initial consultation through final submission.

Absorption Systems Cell Lines

Caco-2 (C2BBe1) OCT2-HEK293 OATP1B3-HEK293 MATE1-HEK293
MDR1-MDCK OAT1-HEK293 OATP1A2-HEK293 MATE2K-HEK293
BCRP-MDCK OAT3-HEK293 OATP2A1-HEK293 BSEP-Vesicles
OCT1-HEK293 OATP1B1-HEK293 OATP2B1-HEK293 MRP2-Vesicles
NTCP-HEK293 PepT1 (C2BBe1) Custom Development  

TECHNOLOGIES AND METHODOLOGIES

Extensively characterized test systems using the most clinically-relevant substrates and inhibitors for complete regulatory confidence.

Cell Line Substrate Inhibitor
MDR1 Digoxin , Etoposide, Fexofenadine, Amprenavir, Talinolol, Loperamide Valspodar, Cyclosporin A, Vinblastin, Ketoconazole, Loperamide
BCRP Cladribine, Topotecan, Prazosin, Cimetidine, Sulfasalazine, Mitoxantrone, Actinomycin D, Doxorubicin, Estrone-3-Sulfate, Etoposide, Irinotecen, Rosuvastatin, Daunorubicin, SN-38, Fexofenadine Ko143, Elacridar, FTC
OCT1 MPP+, Amantadine, Amiloride, Metformin, Pindolol, Procainamide, Propanolol, Ranitidine Repaglinide, Disopyramide, Quinine, Quinidine, Cimetidine, Rosiglitazone, Triethylamine, Metformin
OCT2 MPP+, Pindolol, Ranitidine, Procainamide, Amiloride, Amantadine Imipramine, TPA, Verapamil, Quinidine, Cimetidine, Metformin, Dopamine, Triethylamine
OAT1 PAH, Adefovir, Cidofovir, Furosemide, Lamivudine, Tenofovir, Zidovudine Probenecid, Bumetanide, Novobiocin, Quinaprilat, TEA, Methotrexate, Lamivudine
OAT3 Furosemide, Bumetanide, Cefaclor, Quinaprilat Probenecid, Bumetanide, Novobiocin, Quinaprilat, Rosuvastatin, Naproxen
OATP1B1 Atorvastatin, Rosuvastatin, Pitavastatin Rifamycin SV, Atenolol, Cyclosporin A, Digoxin, Estrone-3-Sulfate, Estradiol-17β Glucuronide, Ketoconazole, Propranolol, Rifampicin, Ritonavir, Rosuvastatin, Taurocholic Acid, Tolbutamide, Verapamil
OATP1B3 Atorvastatin, Pitavastatin, Rosuvastatin Rifamycin SV, Rifampicin, Rosuvastatin, Taurocholic Acid, Ritonavir, Cyclosporin A, Estradiol-17β Glucuronide, Estrone-3-Sulfate, Atenolol, Propranolol, Digoxin
MATE1 Metformin, MPP+, Cimetidine, Amiloride Cimetidine, Atenolol, Triethylamine, Amantadine, Imipramine, Disopyramide, MPP+, Verapamil, Quinidine, Ritonavir
MATE2K Metformin, MPP+, Cimetidine, Amiloride Pyrimethamine, Ondansetron, Quinidine
MRP2 CDCF MK571
BSEP [3H] Taurocholic acid Cyclosporin A, Troglitazone 

REGULATORY CONSIDERATIONS

We follow the latest recommendations and guidelines from the FDA, EMA, and PMDA.

Transporter FDA EMA PMDA Absoprtion Systems Portfolio
P-gp (MDR1)

Caco-2 (C2BBe1), MDR1-MDCK
BCRP

Caco-2 (C2BBe1), MDR1-MDCK
OATP1B1

OATP1B1-HEK293
OATP1B3

OATP1B1-HEK293
OAT1

OAT1-HEK293
OAT3

OAT3-HEK293
OCT1   Consider   OCT1-HEK293
OCT2

OCT2-HEK293
MATE1

Likely

MATE1-HEK293
MATE2K

Likely

MATE2-HEK293
BSEP  

  BSEP-Vesicles

HOW CAN WE SUPPORT YOUR DRUG TRANSPORTER NEEDS?