Qualyst Transporter Solutions is the world's exclusive provider of hepatic drug transporter products and contract research services utilizing the patented B-CLEAR® technology.
With over a decade of experience using our integrated in vitro hepatic model, we can support your hepatic disposition questions. No other hepatic model combines physiologic uptake and efflux transporters with hepatic metabolism. This means that our integrated model, coupled with our experience, can answer your questions about compound clearance, drug transporter interactions, cholestatic and hepatotoxic potential of your compounds.
Transporter Certified™ Hepatocytes
Translating In Vitro Knowledge into In Vivo Solutions
High quality cells are critical for reliable cell-based, assay results. Commercially available hepatocytes vary measurably in quality,
phenotype, and function, though these differences may not always be visibly evident. In other words, hepatocytes that
appear to be the same and express the same level of proteins may not have the same functionality (Figure 1).
Importance of Transporter Certified™
In hepatocytes with no functioning efflux, toxicity can be observed at low, non-physiologic concentrations because uptake continues
to occur (Figure 2). Transport Certified hepatocytes have characterized, physiologic uptake and efflux transport, ensuring
proper intracellular concentrations. Our kits and contract services use Transporter Certified™ hepatocytes that provide a standard
of hepatocyte function and ensure reproducibility from experiment to experiment. Transporter Certified™ hepatocytes can
be used for transporter studies, drug interaction experiments, intracellular concentration determination, induction, metabolism,
hepatotoxicity or any experiment where transporters and in vivo correlation are important.
What is the Transporter Certified™ process?
We perform a rigorous evaluation of human cryopreserved hepatocytes that includes a third party plating and viability assessment as
well as phase II activity. Functionally, we quantitate the level of transporter activity using drug reference probes that focus on
uptake, biliary efflux, and basolateral efflux activities. In addition, we assess the inhibition of these transporters as well as the
intracellular concentrations of these same probes. Because the intracellular concentration is the result of all of the transport activities
working in concert, these values reflects the balance of these functions together. We express this as a Kp ratio that is the
concentration of compound inside the cell to the concentration on the outside. A Kp ratio of 1 indicates that the concentration
inside the cell is the same as outside the cell. Activities that are high or low may still have an appropriate Kp ratio. When uptake
and efflux are out of balance however, the Kp ratio can deviate dramatically, and in some cases, the range of values can be as high
as 100-fold different indicating that transporter activity is not physiologically relevant. These cells are not Certified and should
not be used for any in vivo predictive experiments.
We assess bile acid profiles within the cell since functioning hepatocytes synthesize and transport bile acids. We measure the
various species and verify that the correct ratios of bile acid conjugates are observed. Finally, this information is compared to an
extensive historical database and a defined range of performance is provided for each certification (Figure 3).
The following laboratories have cryopreserved human hepatocytes available that have been Certified to culture out to 5 days
and maintain uptake, biliary and basolateral efflux transporters as well as proper bile cannuliculi formation. Our Transporter
Certified™ Cryopreserved Hepatocyte Partners include:
Hepatocytes and hepatocyte kits are widely available commercially, however, only our Transporter Certified™ partners above
have allowed assessment of their product to verify quality.
Request Transporter Certified™ hepatocytes from your vendor or contact us for more information!
Copyright 2011-2012 Qualyst Transporter Solutions, LLC. All Rights Reserved.B-CLEAR is a registered trademark of Qualyst Transporter Solutions, LLC.
*B-CLEAR® is covered by US Patent 6,780,580 and other worldwide patents issued & pending.