DDI Transporters – Opti-DDI™ Services Panel

Validated DDI transporter assays with submission quality reports and agency approved substrates and inhibitors

Optivia’s Opti-DDI™ Transporter Services Panel provides you with FDA, EMA & PMDA compliant services to help you meet your regulatory requirements. We provide unprecedented transporter assay capability and expertise in transporter DDIs and FDA/EMA/PMDA compliant transporter studies. Our award-winning transporter DDI services include robust validated assays with agency approved substrates and inhibitors, expert advice on study design, and regulatory submission quality reports, as well as guidance on additional transporters the agencies often request.

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 drug-drug interactions (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.

Please contact us to discuss your regulatory transporter study needs.

DDI Transporters for Regulatory Compliance

TransporterFDAEMAPMDAPharmacokinetic relevanceRepresentative substratesRepresentative inhibitors
P-gpintestine absorption, BBB penetration, hepatic and renal clearancedigoxin, quinidine, vinblastine, fexofenadine, atorvastatinelacridar, verapamil, ketoconazole, cyclosporine, ritonavir
BCRPintestine absorption, BBB penetration, hepatic and renal clearanceE17bG, methothrexate, rosuvastatin, sulfasalazine, topotecanKO-143, elacridar, cyclosporine, gefitinib, erlotinib
OATP1B1Hepatic clearanceE17bG, atorvastatin, rosuvastatin, pravastatin, bilirubincyclosporine, rifampicin, gemfibrozil, ritonavir, lopinavir
OATP1B3Hepatic clearanceCCK8, rosuvastatin, pitavastatin, telmisartan, bilirubin cyclosporine, rifampicin, ritonavir, lopinavir, MK-571
OAT1Renal clearancePAH, adefovir, cidofovir, tenofovir, olmesartan probenecid, mefenamic acid, ketoprofen, indomethacin, olmesartan
OAT3Renal clearancePAH, E3S, methotrexate, acyclovir, peniciliin GProbenecid, diclofenic, furosemide, indomethacin, olmesartan
OCT1ConsiderHepatic clearancemetformin, MPP+, TEA, oxaliplatincimetidine, quinidine, disopyramide, rosiglitazone, clonidine
OCT2Renal clearancemetformin, creatinine, TEA, oxaliplatin, famotidinecimetidine, quinidine, dolutegravir, disopyramide, impramine
BSEPHepatic clearance and DILItaurocholate, glycocholate, lithocholate, bosentan, pravastatinrifampicin, cyclosporine, benzbromarone, troglitazone, clofazimine
MATE1LikelyRenal clearancemetformin, creatinine, TEA, oxaliplatin, cimetidinecimetidine, ondansetrone, ritonavir, famotidine, imatinib
MATE2KLikelyRenal clearancemetformin, creatinine, TEA, oxaliplatin, cimetidinecimetidine, mitoxantrone, ondansetrone, nifekalant, imatinib

DDI Transporter Resources

US FDA, Guidance for Industry Drug Interaction Studies —In Vitro Metabolism- and Transporter- Mediated Drug-Drug Interaction Studies (draft guidance), Oct. 2017

European Medicines Agency (EMA), Guideline on the investigation of drug interactions, June 2012

Pharmaceuticals Medical Devices Agency (PMDA) Draft Guideline on Drug Interactions (2013)

Membrane transporters in drug development

Emerging transporters of clinical importance: an update from the International Transporter Consortium

When should in vivo transporter-mediated drug-drug interaction studies be conducted? A scientific perspective