We recommend assessing the rate of hepatic uptake of a test article if data from transporter screening study indicates transporter-mediated uptake occurs. Hepatic uptake assessment studies have the following objectives:
- Estimate Passive vs. Active Uptake
- Estimate Hepatic Accumulation
- Determine if Uptake DDIs Should Be Evaluated
Depending on client preferences and the study design, we implement uptake studies using oil spin suspension or 3-hour plated hepatocytes. Clients may prefer one model versus the other in order to compare study data to their historical data set for the same or other compounds.
Hepatic uptake rate studies include the following deliverables:
- Uptake (pmol/mg)
- Uptake rate, if more than 3 timepoints
To determine a rate of active uptake, the studies are typically conducted either with and without the presence of a pan-inhibitor, or at 370 and 40 C.
We adapt study protocols based on input from our clients about their test article. Typically, we would select a concentration of 1 µM and 6 timepoints.
If multiple species (rat, dog, monkey, human) are required and there is a study objective to compare data amongst species we recommend implementing the study using suspension hepatocytes.