As example: Drug A (Km=2uM), drug B (Km=45 uM). If we do inhibition or DDI study with known inhibitor and found IC50 for drug A is higher than drug B. what will be the explanation of the result (IC50 or Ki) for two drugs (A and B)?
@Ranjita Santra, thank you for the reply. Actually I know about the enzyme kinetics and those facts. There, are several aspects regarding the kinetics and drug-interactions. Scientists has been explained differently in the articles. Although, I am looking for the particular experts opinion of my questions.
My point is, How you will interpret your data if you get two different Ki for two drugs with same inhibitor?
Note: Drug A (Km=2uM), drug B (Km=45 uM). If inhibition or DDI study result found Ki for drug A is 15uM and drug 5uM. what will be the explanation of the result (IC50 or Ki) for two drugs (A and B)?
I was just having a peruse through some DMPK related questions and looked at this out of interest......I know it's a while since the question was posted but just in case it helps.......I'm no expert on enzyme kenetics but I'm not so sure you actually have an issue here, if the Km for drug A is lower than drug B would you not expect the IC of the inhibitor to be higher? The binding of drug A occurs with higher afinity than B and therefore (without knowledge of 'K off' assuming an equal rate of transport for A and B) would require an increased level of inhibitor to reduce transport by half in comparison to B.
Marcus Hanley @ Thank you for the comment. I also assume exactly as you have mentioned. Though, some people was against this explanation though they didn't gave scientific explanation to explain that phenomena. That's why i posted here to see experts opinion :)