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We all know that the equation used to calculate KI and Kinact for MBI is: Kobs=Kinact*KI/(I+KI). And this equation assumes that there is negligible change of I in the incubation period and that loss of enzyme is solely due to inactivation by the inhibitor. So this assumption will bring out questions that if the inhibitor is not very stable when incubated with microsomes, and furthermore, one of its major metabolites also has strong MBI potential, how to calculate the KI and Kinact of the parent compound? How to differentiate if the MBI is caused by the parent drug or by its metabolite?
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You are absolutely right, there are some assumptions (depending on the experimental settings and the nature of inhibitor) while using this equation (Kobs=Kinact*KI/(I+KI)) that are not always met. In such situations getting the correct values needs a more rigorous data analysis, please see the following papers where some of these issues are discussed.
Yang J, Jamei M, Yeo KR, Tucker GT and Rostami-Hodjegan A (2005) Kinetic values for mechanism-based enzyme inhibition: Assessing the bias introduced by the conventional experimental protocol. Eur J Pharm Sci 26:334-340.
Yang J, Jamei M, Yeo KR, Tucker GT and Rostami-Hodjegan A (2007) Theoretical assessment of a new experimental protocol for determining kinetic values describing mechanism (time)-based enzyme inhibition. Eur J Pharm Sci 31:232-241.
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