Interaction Qualified Hepatocytes – advancing in vitro drug interaction testing to the next level

Clinically relevant Drug-Drug interactions (DDI) are a serious concern for any new drug development project.

One of the first steps in identifying the potential for DDI is to determine whether a new developmental drug will cause an increase in expression or activities of cytochrome P450s (CYPs). The mechanisms by which one chemical may increase or inhibit CYPs is through induction of gene transcription or in some cases direct enzymatic potentiation or inhibition. Further to these mechanisms, other DDIs can occur because of increasing or inhibiting the function of cellular drug transporters. In many cases, multiple mechanisms may be working to create potential for DDI.

• Use the same donor for basal clearance, transport, and induction studies
• Actual rates of transport reported rather than relative rates for less ambiguity
• Large lots mean fewer rounds of testing so you can focus on results
• Prequalified in Lonza media for better reproducibility

• Inducibility of enzyme activity for CYP3A4, CYP2B6, and CYP1A2
• Inducibility of mRNA for CYP3A4, CYP2B6, CYP1A2, and CYP2C8 genes
• Actual rate of uptake or efflux for OATP1B1/3, OCT1/2, NTCP, and BSEP¹ transporters
• Differences in passive vs. active uptake for OATP1B1/3, OCT1/2, and NTCP transporters.
• Basal metabolism for 8 CYPs and now including Aldehyde Oxidase
• Plated low-turnover clearance for CYP2C9, CYP2D6, and CYP3A4
• Complementary thawing, plating, and maintenance medium available

Now you can perform all you metabolism and DDI studies, in plated or suspension formats, using our Interaction Qualified hepatocytes for more confidence in results and validity of PBPK models.

Our qualification methods are modelled after recommendations from the FDA publication In Vitro Metabolism and Transporter Mediated Drug-Drug Interaction Studies Guidance for Industry (2017).

1. BSEP efflux activity was measured using method described in Jie Zhang, et al., Chemico-Biological Interactions, Volume 255, 2016, Pages 45-54,