In a few forthcoming posts, I'd like to share several short articles published by Dr Chris Bohl of Sekisui Xenotech, a technical expert in the field of ADME-Tox tools and applications. I feel they may be of special interest to researchers working in the field of ADME-Tox studies.
Today, we'll take a look at compounds that exhibit high metabolic stability in hepatocytes and subcellular fractions (S9, microsomes and cytosol), as these can be a challenge for ADME scientists.
Subcellular fraction test systems are easy to source and to use at the bench, and the methods for xenobiotic metabolism in these matrices are largely standardized and accepted by the scientific community. However, these systems are also limited to a 4-6 hour window of time when they are metabolically active and when they can generate quality data.
There have been many interesting advances in the field to address this constraint, however the complexity, amount of labour and cost involved can make these procedures difficult to establish in your lab. Scientists at Sekisui XenoTech have developed and patented the CryostaX® technology, which combines ease of use and cost effectiveness for examining low-turnover compounds in house. Supported by optimized medium, the pooled, plateable human hepatocytes can be cultured for up to 48 hours without a medium change; giving a significantly extended incubation window in which to collect metabolism data (Fig. 1). When compared to alternative methodologies used to assess low-turnover compound metabolism, CryostaX® generates comparable metabolism data in a format that is easier to use and more cost effective. (Fig. 2).
Figure 1. Metabolic stability of the low clearance drugs dysopyramide, tolbutamide and S-warfarin in pooled plated hepatocytes. Legend: Clint values for 14 compounds with CryostaX® pooled plateable hepatocytes.
Figure 2. Comparable data with other test systems for low turnover drug clearance assessment.The CryostaX® technology enables Sekisui XenoTech’s scientists to create attaching, customizable pools of hepatocytes that have only undergone a single cryopreservation cycle, versus the two cycles that are required for traditional pooling methods, thereby protecting the cells’ drug metabolizing activities by minimizing the cryoinjury brought on by each round of cryopreservation.
If you have particular needs for your ADME-Tox studies, and would like a special custom pool created by us just for you, then let me know as this can be done at no extra cost. Get in touch via the form below, or contact me directly.