Screen Transporter Activity: Inhibition and Substrate

Type:Services
SUBTYPE:Transporter AssaysHepatobiliary Disposition
APPLICATION & SPECIALITY USES:ADME-Toxicology Products and Services
Keywords:B-CLEARB-CLEAR TechnologyBiliary ClearanceBiliary ExcretionHepatic ClearanceTransporters

We conduct hepatic transporter inhibition and substrate studies to provide an early screen for transporter-mediated uptake and disposition as well as potential DDI risk.

Data from transporter screening studies is used to inform additional steps in hepatic disposition programs. If there is little to no hepatic uptake of the test article additional assessments of transporter interactions in hepatocytes may not be necessary in the preclinical program. However, if the data indicates transporter-mediated uptake and / or efflux activity the following evaluations may be important in a preclinical program:

  • Rate of Uptake
  • Hepatic Accumulation
  • Biliary Disposition
  • Disposition DDIs

Deliverables

Our transporter screening studies include the following deliverables:

  • Data report on uptake and efflux of the test article
  • Calculation of inhibition kinetics (IC50), if possible

Study Design

Using our OPTI-EXPRESSION™ Technology, we efficiently express human transporters in MDCK II or CHO polarized mammalian cell monolayers, where they are localized to the appropriate membrane (i.e., apical or basolateral). Our typical screening program includes transporters in our OPTI-Regulatory panel, a selection of transporters that Guidance documents from the EMA and FDA recommend be evaluated for an IND submission transporter screening studies include the following deliverables:

  • Data report on uptake and efflux of the test article
  • Calculation of inhibition kinetics (IC50), if possible