SUBTYPE:Transporter Assays
APPLICATION & SPECIALITY USES:ADME-Toxicology Products and ServicesIND-Enabling Studies

Validated DDI transporter assays using agency-approved substrates and inhibitors to prove submission-quality reports

Our OPTI-REGULATORY Panel provides FDA, EMA and PMDA compliant reports to meet regulatory guidance for transporter drug-drug interaction (DDI) studies. Using our OPTI-EXPRESSION Technology we provide efficient and consistent investigations of potential transporter effects of new drugs. Our research services include robust validated assays with substrates and inhibitors that are accepted by regulatory agencies. By working with us, our clients take advantage of our experience and expertise in study design and regulatory submissions; additionally, our scientists provide guidance on additional transporter studies the agencies often request.

In our standard programs we evaluate the test article at a single concentration in triplicate. Compounds determined to be potential inhibitors may be assessed in a follow-on study to determine an inhibition curve and IC50.

DDI Transporters for Regulatory Submissions

Transporters expressed throughout the body affect the plasma and tissue concentrations of a variety of drugs. In particular, uptake and efflux transporters expressed in the intestine, liver, and kidney have been implicated in a variety of serious DDIs. The US FDA, European Medicines Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) request in vitro studies be conducted on the transporters listed below for DDI assessment and drug labeling. Each agency has published DDI guidance documents that differ slightly in recommended transporters to be tested, in vitro study design and data interpretation.

TransporterFDAEMAPMDAPharmacokinetic relevanceRepresentative substratesRepresentative inhibitors
BCRPIntestinal absorption, BBB penetration, hepatic and renal clearanceE17bG, CCK-8,
methothrexate, prazosin,
rosuvastatin, sulfasalazine, topotecan
Ko143, chrysin,
elacridar, cyclosporine, gefitinib, erlotinib
BSEPHepatic clearance and DILITaurocholate, glycocholate, lithocholate, bosentan, pravastatinRifampicin, cyclosporine, benzbromarone, troglitazone, clofazimine
MATE1LikelyRenal clearanceMetformin, creatinine, TEA, oxaliplatin, cimetidineCimetidine, ondansetrone, ritonavir, famotidine, imatinib
MATE2-KLikelyRenal clearanceMetformin, creatinine, TEA, oxaliplatin, cimetidineCimetidine, mitoxantrone, ondansetrone, nifekalant, imatinib
OAT1Renal clearancePAH, adefovir, cidofovir, tenofovir, olmesartanProbenecid, mefenamic acid, ketoprofen, indomethacin, olmesartan
OAT3Renal clearancePAH, E3S, methotrexate, acyclovir, peniciliin GProbenecid, diclofenic, furosemide, indomethacin, olmesartan
OATP1B1Hepatic clearanceE17bG, atorvastatin, rosuvastatin, pravastatin, bilirubinCyclosporine, rifampicin, gemfibrozil, ritonavir, lopinavir
OATP1B3Hepatic clearanceCCK8, rosuvastatin, pitavastatin, telmisartan, bilirubinCyclosporine, rifampicin, ritonavir, lopinavir, MK-571
OCT1ConsiderHepatic clearanceMetformin, MPP+, TEA, oxaliplatinCimetidine, quinidine, disopyramide, rosiglitazone, clonidine
OCT2Renal clearanceMetformin, creatinine, TEA, oxaliplatin, famotidineCimetidine, quinidine, dolutegravir, disopyramide, impramine
P-gpIntestinal absorption, BBB penetration, hepatic and renal clearanceDigoxin, quinidine, vinblastine, fexofenadine, atorvastatinElacridar, verapamil, ketoconazole, cyclosporine, ritonavir