Tuesday, 30 July
BioIVT Industry-Sponsored Symposium

 

Potential Benefits of a Physiologically-Relevant Whole Cell Model to Assess CYP Inhibition with Complex Mixtures

Speaker: Amy L. Roe, PhD, DABT

Time: 17:30 - 18:30

Educational Needs Statement: Conventional in vitro methods to assess hepatic enzymatic activity may be inadequate if they do not account for transporter-mediated uptake and efflux, and regulatory pathway effects. Whole cell models can provide a more physiologically-relevant prediction of potential toxicity and drug interaction effects.

Learning Objectives:

  • Compare data from pooled human liver microsomes to a sandwich-cultured human hepatocyte (SCHH) model in a study that assessed potential inhibition of CYP3A4/5and CYP2C9 enzymatic activity by Boswellia serrata extract.

  • Demonstrate methods to predict botanical-drug interactions (BDIs) that are potentially applicable to drug-drug interactions (DDIs)

  • Discuss benefits of SCHH models to study complex mixtures such as botanicals.

Who Should Attend?

  • Researchers using in vitro models to predict potential toxicological, ADME, PK, and other effects of drugs in development, and other chemicals and natural ingredients.

Abstract:

We will present results from a published study (Roe et. al., 2019 AIVT) to evaluate potential inhibition of CYP3A4/5 and CYP2C9 enzymatic activity by Boswellia serrata extract (BSE) using pooled human liver microsomes (PHLM) and a more physiologically-relevant sandwich-cultured human hepatocytes (SCHH) model. In the scientific literature, BSE has been shown to reduce the activity (55% to ?65%) across major CYP450 enzymes, including CYP3A4/5 and CYP2C9, using baculovirus-infected insect cells. These reported results, contrasted with a seemingly history of safe use of BSE, led us to question the relevance of the PHLM model. We will show that potent CYP3A4/5 and CYP2C9 inhibition observed for BSE in microsomal systems was not observed in SCHH. SCHH are particularly useful for studying complex mixtures such as botanicals and are an effective model to evaluate BDI and DDI.