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 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.
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
- 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.
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 |
