Abstract
Potential induction of cytochrome P450 (CYP) by a new chemical entity (NCE) is a required assessment in small molecule drug discovery and development. CYP induction-mediated drug–drug interactions (DDI) can lead to decrease therapeutic efficacy, decreased exposure of concomitant medication, and an increase in activity or reactive metabolites leading to toxicity. Industrywide, CYP1A2, CYP2B6, and CYP3A are commonly assessed for induction via nuclear receptors aryl hydrocarbon (AhR), constitutive androstane (CAR), and pregnane X (PXR), respectively. Although cell lines are often used, because they lack native receptors, enzymes, uptake and efflux transporters, the current gold standard is cultured human hepatocytes. Cryopreserved hepatocytes are more readily available and offer the flexibility of donor selection and advanced experiment planning. This chapter describes the general methodologies used to determine CYP induction via mRNA expression and CYP enzyme activity using cryopreserved human hepatocytes.
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Wong, S. (2021). Determination of In Vitro Cytochrome P450 Induction Potential Using Cryopreserved Human Hepatocytes. In: Yan, Z., Caldwell, G.W. (eds) Cytochrome P450. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1542-3_12
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DOI: https://doi.org/10.1007/978-1-0716-1542-3_12
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