A NOVEL READY-TO-USE SYSTEM FOR IN VITRO NET TRANSPORT EVALUATION
Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. Monolayer assays using transfected MDCKII cells have been widely recognized tools, acknowledged by the ITC1, to study the interaction of drugs with cellular transporters.
OAT1 – Organic Anion Transporting 1 is primarily expressed in the basolateral membrane of proximal tubule cells in the kidneys; and BCRP – Breast Cancer Resistance Protein plays an important role in drug disposition and distribution, similar to P-gp.
PreadyPortTM-OAT1/BCRP Kits contain 24-insert integrated plates with differentiated MDCKII cells expressing OAT1/BCRP, as well as the parental cell line. It can be used to model the net transport events of important fluid compartment barriers in the organism. This system is suitable for performing both inhibition and substrate assessments.
- Available on demand
- User-friendly and easy-handling system
- Adaptable to automation
- Transporter experiments without in house cell propagation
- Transporter experiments without in house cell line development or acquisition
- OAT1/BCRP substrates assessments (direct transport studies)
- OAT1/BCRP inhibition assessment (drug-drug interactions)
- Models the net transport events of barriers like; intestinal epithelia, blood-brain barrier and kidney
- OAT1 has relevance to renal drug clearance, drug disposition and interactions. The FDA and EMA require that the drug-drug interaction liability of this transporter be evaluated in vitro for drug candidates that are renally eliminated.
- BCRP transporter has relevance to drug PK and interactions, for BBB and tumor penetration. In vitro evaluation is required by the regulatory agencies FDA and EMA for all drug candidates prior to going to market.
- OATs are critical to the entry of many drugs into the renal proximal tubules and for renal excretion.
- Decrease in renal secretion and clearance may produce an increase in systemic drug exposure, thereby resulting in clinically significant changes in the overall drug PK.
- Clinically relevant changes in clearance of therapeutics can occur when OAT1 transporter activity is inhibited.
- BCRP interaction can act as a barrier to absorption and distribution of drugs in intestinal epithelia and blood-brain barrier. BCRP also contributes to the biliary excretion of compounds.
- Inhibition of BCRP may lead to hepatotoxicity due to build-up of endogenous and xenobiotic compounds in the liver.
- Several clinicaly relevant drug-drug interactions (DDIs) have been associated with BCRP.