We can support you with the safety evaluation required for investigational new drugs by providing comprehensive, fully regulatory compliant in vitro assays to address questions related to drug interactions. Our scientific team is available also to help you with the assay design and data interpretation.
Would you like to get more familiar with the topic first? Please check out our e-books, written by our scientific experts on the field. The e-books can be accessed from our material portal.
Evaluating metabolism-mediated drug interactions
Comprehensive CYP reaction phenotyping includes combination of two approaches; liver microsomes coupled with CYP selective inhibitors, and with recombinant CYPs – with or without metabolite identification. Our portfolio includes also assays to elucidate involvement of several non-CYP enzymes in metabolism of the investigated compound.
For evaluating CYP inhibition, we provide a cocktail approach for determining inhibition of all the major drug metabolizing CYP enzymes within a single incubation, delivering IC50 and IC50 shift values. As a follow-up assay, single enzyme incubations are performed for accurate determination of parameters Ki, Kinact/KI, if necessary.
The three most important enzymes CYP1A2, 2B6 and 3A4 are typically initially addressed when determining CYP induction potential, primarily at mRNA level, but also enzyme activity measurement can be included. Importantly, CYP2C and UGT enzyme induction can be investigated, too.
Services for evaluating transporter-mediated drug interactions
Our transporter services includes panel of all the transporters, which are relevant from the drug-interaction perspective. For evaluating efflux-transporter inhibition, two complementary approaches are available: namely vesicular uptake and cell monolayer permeability (MDCKII) assays. Uptake transporter assays are performed with HEK293 cells, transfected with a single transporter. The protocols follow the guidance from FDA and EMA.
Importantly, a broad selection of supporting assays is available, such as solubility screening in the test conditions, determination of plasma protein binding and unbound fraction in the incubations.
Do you have questions? Why don’t you get in touch and we can have a call to discuss how we could help you?
