How Can We Help?
Skip to content
Lab technician with dropper into lab test tubes

In Vitro Drug Transporter Services to Support Preclinical Drug Development

We offer definitive in vitro transporter studies to determine substrate and inhibition potential of a drug candidate with clinically-relevant transporters using validated, industry-accepted test systems. Definitive in vitro Drug Transporter Substrate & Inhibition studies use regulatory guidance-compliant test systems and study designs to investigate a compound’s potential to interact with known uptake (SLC, solute carrier) and efflux (ABC, ATP binding cassette) transporters, precipitating a potential drug-drug interaction (DDI).

Our Approach to Drug Transport

Transporters have become increasingly important in drug development due to the major role they play in absorption, distribution and excretion (ADME) of endogenous and exogenous compounds. Additionally, potential for transporter-mediated drug-drug interactions (DDI) is associated with potential toxicological and pharmacological consequences. As evidenced in numerous publications, the effects of transporters on the pharmacokinetics of several drugs, and associated DDI, have been reported. Consequently, recent guidance documents released by the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and Pharmaceuticals & Medical Devices Agency (PMDA) of Japan emphasize the importance of evaluating the potential of new drug candidates for transporter-mediated DDI with a determination of victim (substrate) and perpetrator (inhibition) potential.

A small molecule enters a cell via drug transporters in the cell membrane

In Vitro Preclinical Transporter Assays We Offer

Our team conducts the following assays to evaluate your drug candidate’s interaction with drug transporters:

Substrate potential assays are designed to address the FDA’s directive to “determine if the investigational drug is a substrate of a transporter,” to inform risk of DDI potential, explain observations of increased toxicity or altered efficacy, and to determine if clinical investigation is necessary.

Drug Transporter Inhibition assays are designed to address the FDA’s directive to “determine if the investigational drug is an inhibitor of a transporter,” in order to evaluate capacity to act as a perpetrator in potential transporter-mediated DDIs.

Uptake & Efflux Study Options

We work with both uptake (SLC) and efflux (ABC) transporters in different test systems and assay designs according to regulatory guidance:

See Our Drug Transporter Portfolio of all the different efflux and uptake transporters we offer, organized within two major superfamilies: ABC (ATB binding cassette) and SLC (solute carrier).

Uptake Transporter assays assess SLC (solute carrier) transporter families for potential drug-drug interactions involving the drug candidate as a substrate or inhibitor of relevant uptake transporters using appropriate transporter-expressing cells as a test system.

Efflux Transporter assays assess ABC (ATP binding cassette) transporter families for potential drug-drug interactions involving the drug candidate as a substrate or inhibitor of relevant efflux transporters using appropriate test systems.

Features of Our Drug Transport Study Design

  • An extensive selection of transporters and assays
  • Multiple test systems for the major transporters, from membranes to in vivo models
  • Expert guidance for compound development custom-designed for your needs
  • Communication and review of all study materials performed by a study director

Known Clinically Relevant Transporter DDIs

The following charts show a partial list of compounds that have been implicated in transporter-based clinically relevant drug-drug interactions as either a substrate or inhibitor.

P-gp Transporter

INHIBITORSSUBSTRATES
Clarithromycin
Cyclosporine
Erythromycin
Itraconazole
Quinidine
Ritonavir
Telithromycin
Verapamil
Aliskiren
Digoxin
Docetaxel
Fexofenadine
Paclitaxel
Ritonavir
Talinolol
Vinblastine

BCRP Transporter

INHIBITORSSUBSTRATES
Elacridar (GF120918)Pitavastatin
Rosuvastatin
Topotecan

OATP1B1 Transporter

INHIBITORSSUBSTRATES
Atazanavir
Clarithromycin
Cyclosporine
Gemfibrozil
Glibenclamide
Lopinavir
Rifampin
Bosentan
Cerivastatin
Pravastatin
Rifampin
Rosuvastatin
Simvastatin
Valsartan

OATP1B3 Transporter

INHIBITORSSUBSTRATES
Atazanavir
Clarithromycin
Cyclosporine
Gemfibrozil
Lopinavir
Rifampin
Bosentan
Paclitaxel
Pravastatin
Rifampin
Rosuvastatin
Valsartan

OATP2B1 Transporter

INHIBITORSSUBSTRATES
Cyclosporine
Gemfibrozil
Quercetin
Grapefruit juice
Orange juice
Aliskiren
Atorvastatin
Pravastatin
Pitavastatin
Rosuvastatin

OATP1A2 Transporter

INHIBITORSSUBSTRATES
Verapamil
Naringin
Quercetin
Grapefruit juice
Orange juice
Atenolol
Celiprolol
Ciprofloxacin
Fexofenadine
Pravastatin

OAT1 Transporter

INHIBITORSSUBSTRATES
Indomethacin
Mycophenolate
Olmesartan
Probenecid
Adefovir
Captopril
Cidofovir
Furosemide

OAT3 Transporter

INHIBITORSSUBSTRATES
Gemfibrozil
Indomethacin
Mycophenolate
Olmesartan
Probenecid
Salicylate
Benzylpenicillin
Cefotiam
Furosemide
Methotrexate
Olmesartan
Pravastatin

OCT2 Transporter

InhibitorsSubstrates
Bisoprolol
Carvedilol
Cimetidine
Procainamide
Ranitidine
Trimethoprim
Amatadine
Cimetidine
Cisplatin
Lamivudine
Metformin
Ranitidine

MATE1 Transporter

INHIBITORSSUBSTRATES
Cimetidine
Pyrmethamine
Quinidine
Rapamycin
Cephalexin
Cimetidine
Metformin
Procainamide

Planning Your Drug Transporter Studies

To plan transporter studies it is best to work backwards from FDA clinical guidance since timing is not explicitly mentioned in the in vitro guidance form 2020. The guidance says that before a drug is to be administered to patients in clinical trials, there should be “enough DDI information to prevent patients from being unnecessarily excluded.” 

The International Transporters Consortium (ITC) recommends that the choice of transporters to be investigated should be driven by scientific evidence, and should be evaluated either prospectively or retrospectively as described in published literature or guidance. For example, hepatic OCT1 is recommended for prospective evaluation for inhibition and substrate potential, and intestinal OAT2B1 is recommended for retrospective evaluations in specific instances of DDIs. OAT2 is recognized to be an important transporter in the uptake of some high permeability acidic and zwitterionic drugs (Extended Clearance Classification System (ECCS) Class 1A), but evidence is lacking for a specific recommendation so drug developers are encouraged to “follow the evidence” to plan studies. Read more about current regulatory expectations and emerging transporters of importance in a digest of our 2019 Drug Transporters Webinar.

Transporters, in concert with metabolizing enzymes, can govern a drug’s disposition and pharmacological action. Conversely, a drug can also modulate transporter expression or activity, resulting in altered disposition of endogenous (e.g., creatinine, glucose) or exogenous substances

FDA 2020 “In Vitro Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry”

Drug Transporter Related Resources:

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.

There’s a lot to choose from

We’re proud to offer you the widest selection of options available when it comes to your transporter studies

Services 7

Which transporters could your compound interact with?

When considering follow-up actions to testing compounds as substrates and inhibitors of drug transporters, use our decision tree to make smart choices

Drug Transporter