Cytochrome P450 and UGT induction studies to predict drug-drug interaction.
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Robust Dynamic Range to Assess Induction Response
Flexibility to use multiple inducers or assays for the same enzyme with robust analytical sensitivity. Mean and standard deviation of fold induction of enzyme activity in 3 donors after treatment of 50 μM omeprazole (OME), 20 μM ß-naphthoflavone (BNF), 1 mM phenobarbital (PB), or 10 μM rifampicin (RIF). Enzyme activities measured were phenacetin O-deethylase, S-mephenytoin N-demethylase, bupropion hydroxylase, amodiaquine N-deethylase, diclofenac 4’-hydroxylase, S-mephenytoin 4’-hydroxylase, and testosterone 6ß-hydroxylase.
Reproducible Induction Response in Gentest® Inducible-qualified Human Cryo-hepatocytes
Omeprazole-induced CYP1A2 catalytic activity in Gentest® Inducible-qualified human cryo-hepatocytes on 7 independent days
Highly reproducible, robust data. Phenacetin O-deethylase activity in a single donor (lot 246) of Gentest® Inducible-qualified human cryopreserved hepatocytes in 7 independent experiments conducted over the span of 18 weeks. Cells were treated with 50 μM omeprazole (OME) for 2 days prior to determination of enzyme activity. The amount of acet- aminophen metabolite formation was determined by incubating cells with 100 μM phenacetin for 30 minutes.
Zhang JG, et al (2014). Evaluation of calibration curve-based approaches to predict clinical inducers and non-inducers of CYP3A4 with plated human hepatocytes. Drug Metab. Dispos. 42:1379-1391.
Wong, S.G. et al (2021). Considerations from the innovation and quality induction working group in response to drug-drug interaction guidance from regulatory agencies: Guidelines on model fitting and recommendations on time course for in vitro cytochrome P450 induction studies including impact on drug interaction risk assessment. Drug Metab. Dispos. 49:94-110.
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