Drug Transporter Services

Why evaluate the substrate and inhibitor potential of the investigational drug 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.

Transporter Categories

Bile Salt Export Pump (BSEP)
Breast Cancer Resistance Protein (BCRP)
Multidrug and Toxin Extrusion (MATE)
Multidrug Resistance-Associated Protein (MDR)
Organic Anion Transporter (OAT)
Organic Anion Transporter Polypeptides (OATP)
Organic Cation Transporter (OCT)

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.

Premium quality expression systems for superior accuracy and precision

Transporter Evaluation Systems

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  

Regulatory Requirements

CellPort Assay Services

Off-the-shelf and custom designs for maximum utility at every stage of development

  Discovery/IND-Enabling Definitive/NDA-Enabling
DESIGN    
System Compatibility None Comprehensive
Assay Rigor Basic Advanced

ASSESSMENTS
   
Substrate Single Concentration Multiple Concentrations, Inhibitor Challenge, Km/Vmax
Inhibition Single Concentration Multiple Concentrations, IC50

CellPort Validation

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 

 

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New 5th Edition Transporter Reference Guide