ADME Transporters – Opti-ADME™ Services Panel

ADME

Optivia’s Opti-ADME™ Transporter Services Panel consists of major transporters that affect ADME properties of a variety of drugs. Studying these ADME transporters will help you glean a better understanding of drug bioavailability, tissue distribution, excretion, and inter-individual variability in drug responses. Optivia offers a wide range of services for the Opti-ADME panel, ranging from low-cost, rapid screening to more extensive, regulatory-compliant transporter studies.

In vitro ADME (Absorption, Distribution, Metabolism and Excretion) studies have long played a critical role in optimizing both pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs, thereby decreasing attrition rates in drug development. Because transporters regulate the cellular entry and exit of most small molecules, they are critical determinants of every aspect of drug ADME properties. In particular, many new molecular entities (NCEs) synthesized today are hydrophilic compounds with low cell membrane permeability, which are more dependent on transporters to achieve acceptable bioavailability, desirable tissue distribution, and optimized PK profiles.

Please contact us for more information on the Opti-ADME™ panel and how Optivia can help enhance your ADME studies.

Major Transporters Affecting Drug Absorption, Distribution, Metabolism, and Excretion

TransporterGeneRelevance to drug ADMERepresentative substratesRepresentative inhibitors
P-gp/MDR1ABCB1Intestinal efflux, biliary and tubular secretion, BBB effluxdigoxin, quinidine, vinblastine, fexofenadine, atorvastatinelacridar, verapamil, ketoconazole, cyclosporine, ritonavir
BCRPABCG2Intestinal efflux, biliary and tubular secretion, BBB effluxE17bG, methothrexate, rosuvastatin, sulfasalazine, topotecanKO-143, elacridar, cyclosporine, gefitinib, erlotinib
OATP1B1SLCO1B1Hepatic uptakeE17bG, atorvastatin, rosuvastatin, pravastatin, bilirubincyclosporine, rifampicin, gemfibrozil, ritonavir, lopinavir
OATP1B3SLCO1B3Hepatic uptakeCCK8, rosuvastatin, pitavastatin, telmisartan, bilirubin cyclosporine, rifampicin, ritonavir, lopinavir, MK-571
OAT1SLC22A6Renal uptakePAH, adefovir, cidofovir, tenofovir, olmesartan probenecid, mefenamic acid, ketoprofen, indomethacin, olmesartan
OAT3SLC22A8Renal uptakePAH, E3S, methotrexate, acyclovir, penicillin GProbenecid, diclofenic, furosemide, indomethacin, olmesartan
OCT2SLC22A2Renal uptakemetformin, creatinine, TEA, oxaliplatin, famotidinecimetidine, quinidine, dolutegravir, disopyramide, impramine
BSEPABCB11Biliary secretiontaurocholate, glycocholate, lithocholate, bosentan, pravastatinrifampicin, cyclosporine, benzbromarone, troglitazone, clofazimine
MATE1SLC47A1Tubular and biliary secretionmetformin, creatinine, TEA, oxaliplatin, cimetidinecimetidine, ondansetrone, ritonavir, famotidine, imatinib
MATE2KSLC47A2Tubular secretionmetformin, creatinine, TEA, oxaliplatin, cimetidinecimetidine, mitoxantrone, ondansetrone, nifekalant, imatinib
MRP1ABCC1Intestinal absorption, BBB effluxE17bG, E3S, Methotrexate, PAHMK571, Indomethacin, Cyclosporine, Curcumin
MRP2ABCC2Biliary and tubular secretion, intestinal and BBB effluxE17bG, DHEAS, Methotrexate, PAH, IrinotecanMK571, Benzbromarone, Indomethacin, Cyclosporine, Ketoprofen
MRP3ABCC3Intestinal absorption, hepatic effluxE17bG, Fexofenadine, Methotrexate, Folic acidMK571, Taurocholate
MRP4ABCC4Tubular secretion, hepatic efflux, BBB effluxE17bG, DHEAS, Methotrexate, cAMP, cGMP, topotecanMK571, Benzbromarone, Indomethacin, Ketoprofen
MRP5ABCC5BBB effluxMethotrexate, cAMP, cGMP, 5F-dUMPMK571, Benzbromarone, Glyburide, Zaprinast, Sildenafil
OCT1SLC22A1Hepatic uptakemetformin, MPP+, TEA, oxaliplatincimetidine, quinidine, disopyramide, rosiglitazone, clonidine
OCT3SLC22A3Renal uptakemetformin, MPP+, serotonin, histamine, epinephrine
quinidine, prazosin, famotidine, desipramine, lansoprazole
OCTN1SLC22A4Tubular reabsorptionergothioneine, ipratropium, TEA, acetylcholineverapamil, pyrilamide, quinidine
OCTN2SLC22A5Tubular reabsorptioncarnitine, ipratropiumverapamil, emetine
OAT2SLC22A7Renal uptakecGMP, creatinine, paclitaxel, prostaglandin E2, 5-FUindomethacin, cimetidine, piroxicam, diclofenac
OAT4SLC22A11Tubular reabsorptionE3S, uric acid, prostaglandin E2, methotrexateindomethacin, telmisartan, olmesartan, ethacrynic acid
OATP1A2SLCO1A2Intestinal and BBB uptakeE3S, fexofenadine, rosuvastatin, pitavastatin, almotriptanbromosulfophthalein, ritonavir, verapamil, hesperidin, rifamipicin
OATP2B1SLCO2B1Intestinal, hepatic and BBB uptakeE3S, pitavastatin, rosuvastatin, fexofenadine, glyburidebromosulfophthalein, ritonavir, MK-571, cyclosporine, rifampicin
NTCPSLC10A1Hepatic clearancetaurocholate, cholate, glycourodeoxaycholate, rosuvastatin, pitavastatincyclosporine, bosentan, bromsulphthalein, benzbromarone, troglitazone
ASBTSLC10A2Intestinal uptakecholate, taurocholate, glycodeoxycholate, glycochenodeoxycholateNaCDC, elobixia, LUM001, SHP626, A4250, GSK2330672
PEPT1SLC15A1Intestinal uptake, tubular reabsorptionvalacyclovir, glycylsarcosine, oseltamivirlosartan, valsartan, fosinopril
PEPT2SLC15A2Tubular reabsorptionglycylsarcosine, cefaclor, amoxicillinlosartan, valsartan, kyotorphin
ENT1SLC29A1Hepatic, renal, intestinal and BBB uptakeadenosine, ribavirin, gemcitabine, cytarabine, decitabine, 5-FUNBMPR, dilazep, dipyridamole, gefitinib, vandetanib
ENT2SLC29A2Hepatic, renal, intestinal and BBB uptakedecitabine, cytarabine, mercaptopurine, fludarabine, 5-FUdilazep, soluflazine
ENT4SLC29A4Intestinal uptakeadenosine, uridine, metformin, serotonin, azacitidinedeynium-22, trazodone, dyprydamole
CNT1SLC28A1Intestinal uptake, tubular reabsorptionuridine, gemcitabine, cytarabine, lamivudine, zalcitabine, zidovudineclofarabine, vandetanib, gefitinib
CNT2SLC28A2Intestinal uptake, tubular reabsorptionuridine, fludarabine, didanosine, ribavirin, cladribineribavirin, vandetanib

ADME Transporter Resources

US FDA, Guidance for Industry Drug Interaction Studies —Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations (draft guidance), Feb. 2012

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

Membrane transporters in drug development

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

UCSF-FDA transportal database

Bioparadigm SLC transporter database

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

Transporter Interactions in the ADME Pathway of Drugs