As ADME in vitro models are not just about human, mouse or rat hepatocytes and liver cell fractions, it’s important to have access to readily available sourcing for more seldom used models or tissues. Sekisui Xenotech can easily meet these demands with their Custom Products Division who has extensive experience preparing hepatocytes, subcellular fractions and other cells from a wide variety of species and tissue. The project can be fully customized for your particular needs, with the species, organ and characterization of your choice. Alternatively, you can benefit from the surplus list from previous extractions at competitive pricing and short time frame. I tell you a bit more about the 2 options in this post, and give you direct access to the current surplus inventory list. You may find what you are looking for in there!
Pooled human hepatocytes are a preferred test system in many drug discovery and development applications requiring intact cellular systems for in vitro testing. Intact hepatocytes contain the major hepatic drug-metabolizing enzymes and co-factors required to effectively evaluate the metabolism and potential drug-drug interactions of drug candidates.
Over the last decade, improvements in cryopreservation technologies have made using cryopreserved human hepatocytes more convenient. Pooled cryopreserved hepatocytes reduce the inter-individual differences and polymorphic distribution of liver enzymes. However, it’s crucial to carefully select a pool according to its performance but also the application it is to be used for.
Hearing about results from other researchers is always interesting – we’d like to share a testimonial from our first customer using Human Liver Lysosomes. You can get an idea of how these performed in their experiments.
“Our experiments went fantastically well – we see some potential in the material as a tool to generate metabolites of interest in higher yields than the typical systems. See attached a snapshot of one experiment where we incubated a X compound in development with Hepatocytes, Microsomes and the Lysosomes you provided us with. With Lysosomes we were able to generate a metabolite (M6) with significantly higher yields and this is great because it may be a useful tool to allow full characterization of metabolites”
Learn more about Human Liver Lysosomes here: Opening a new era in catabolism models
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EMA Guidance on transporters (Click to view)
Transporters have become increasingly important in drug development due to the major role they play in absorption, distribution and excretion of endogenous and exogenous compounds, as transporter-mediated drug-drug interactions (DDI) are associated with potential toxicological and pharmacological consequences. As shown in numerous publications, the effects of transporters on the pharmacokinetics of several drugs and associated DDI have been reported. Consequently, recent guidance documents released by the US FDA and European Medicines Agency (EMA) emphasize the importance of evaluating the potential of new drug candidates for transporter-mediated DDI.
Solute carrier (SLC) transporters are located in the small intestine, liver, kidney, blood-brain barrier, and so on. They play a role in the up-take of various drugs, as well as endogenous nutrients into cells and thus may influence the ADME properties of, or indeed adverse reactions to, a compound of interest. Thus, investigation of SLC transporters is expected to be helpful during drug development.