Dear all,
I'm checking the effects of the combination between two compounds in an asthma mouse model. During metabolism, these two compounds shared some similar cytochromes, such as CYP2C9, CYP3A4. However, one compound is metabolized mainly by Cytochrome P4502C8 (CYP2C8), and the other one is an inhibitor of CYP2C8.
So, we want to check if we use two compounds separately, at least 6 hours apart, is there any possible interaction between them? Can you give me any advice on that?
Thank you,
Best regards,
Tu Trinh
Invivo drug interaction can be studied with measure of upregulation or down regulation of CYP450 enzymes. Post drug ingestion, enzymatic up-regaulation or vice versa have to be measured every time. Thats may be a possible way.
Animal models are suboptimal for checking drug-interactions with regard to relevance in vivo in human (if this is your major interest).
Sharing similar CYPs is normally not a problem when combining two drugs as long as effective concentrations are below saturating concentrations. Therapeutic concentrations are normally in the nmolar range. When combining two drugs that are both metabolized by the same enzyme, the enzyme is more active under combination. If one drug is an inhibitor and the other a substrate the interaction effect depends on the affinities of the compounds and the concentrations that are used. It would be helpful if you have information on Ki and Km on the compounds. Then you may suggest if there will be an interaction.
Best regards
Christoph
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