December 2017

What to Do with Microsome Stable, Low-Turnover Compounds

Author:  Dr. Chris Bohl
Posted:  07 December 2017

Compounds that exhibit high metabolic stability in hepatocytes and subcellular fractions (S9, microsomes and cytosol) can be a challenge for ADME scientists. These in vitro drug metabolism test systems are easy to source and 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 can generate quality data.

There have been many interesting advances in the field to address this constraint, however the complexity, amount of labor and cost involved can make these procedures difficult to establish in your lab. Scientists at Sekisui XenoTech have developed and patented CryostaX® technology, which combines ease of use and cost effectiveness for examining low-turnover compounds in house. Supported by Sekisui XenoTech’s optimized medium, 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).

CryostaX hepatocytes can be cultured much longer than traditional test systems CryostaX® generates comparable metabolism data in a format that is easier to use and more cost effective
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.

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.

View our CryostaX® human hepatocyte products
Read more about the patented CryostaX® technology
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