This article explores the vital role of hepatocytes in drug development, highlighting their importance in ADME/DMPK studies. It discusses the advantages of primary hepatocytes over subcellular fractions, emphasizing their functional pathways and ability to provide a comprehensive view of drug metabolism.
Sponsored Content by BioIVTReviewed by Aimee MolineuxOct 3 2024 Hepatocytes , the functional parenchymal cells of the liver, are essential for scientists studying absorption, distribution, metabolism, and excretion , as well as drug metabolism and pharmacokinetics . These cells play a crucial role in detoxifying the body and are responsible for metabolizing the majority of xenobiotic compounds.
Advantages of hepatocytes over hepatic subcellular fractions Primary hepatocytes are regarded as the gold standard for ADME and DMPK studies, as they are considered the most representative in vitro test system. Their enzymatic activities are particularly valuable for drug development, and because these cells remain viable, they maintain functional biochemical pathways that subcellular fractions cannot replicate.
Selecting the right hepatocytes for a study It is important to note that not all hepatocyte formats are appropriate for use in all assays. Specific hepatocyte products have inherent characteristics that make them better suited for certain assays. If you are looking for immortalized cells, there are several cell lines available. BioIVT offers the Fa2N-4 immortalized cell line.
However, to fully leverage the benefits of cryopreserved hepatocytes, labs need access to ultra-low temperature storage and tissue culture equipment for thawing and handling the cells. Individual versus pooled donors Individual donor hepatocytes are cells sourced from a single donor’s tissue while pooled hepatocytes are comprised of a mixture of different individual tissue donors’ cells in a single vial.
Selecting the most appropriate primary hepatocytes Researchers using cryoplateable hepatocytes should confirm that these hepatocytes form an appropriate monolayer and that this monolayer is sustained throughout the duration of the planned experiment. Not all lots are suitable for every assay, so data sheets offer essential information to help researchers select the most appropriate hepatocyte lots for their experiments, such as the relevant CYP activity levels, yield, uptake, viability, induction, and monolayer formation capacity.
Pooled hepatocyte products, comprising multiple human donors, are highly suited for use in IND-enabling drug metabolism studies. Using pooled products in these assays is advisable, as it reduces the risk of skewed metabolism data due to donor-dependent variability. Models leveraging HEPATOPAC® technology provide critical data that cannot be obtained from models using plated, suspension, or sandwich-culture hepatocytes. The micropatterned architecture of HEPATOPAC® cultures also enhances consistency and reproducibility compared to random hepatocyte co-cultures.
Drug Development ADME DMPK Hepatocytes Cell Biology
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