The Michaelis constant (KM) and the theoretical maximum process rate (Vmax) are vital parameters in the Michaelis-Menten equation, central to many biochemical reactions. They provide essential insights into enzyme kinetics and drug metabolism.
These parameters can be estimated by analyzing plasma concentration data post-drug administration. A notable example of this application is phenytoin, a drug with capacity-limited kinetics. It's recommended that phenytoin should be administered at two different dose regimens until a steady-state concentration (Css) is reached.
A direct linear plot method determines the KM and Vmax in phenytoin-administered patients. This involves plotting two steady-state concentrations (Css) and their corresponding dosing rates (DR). The lines formed by joining these points are then extrapolated to obtain the values for KM and Vmax.
Several other methods can also be employed to estimate these parameters. One such method is the Lineweaver Burk plot, which plots the reciprocal of the dosing rate versus the steady-state concentration. In this plot, the slope of the line is equal to KM/Vmax, and the y-intercept is 1/Vmax. This means that both parameters can be readily estimated from this plot.
Another method involves plotting the dosing rate (DR) against the ratio of the dosing rate to the steady-state concentration (DR/Css). This method, typically referred to as the Eadie-Hofstee plot, allows for determining both KM and Vmax. The slope of the line obtained from this plot is -KM, while the y-intercept is Vmax.
It's important to note that in clinical settings, the value of KM can vary among patients. Typically, patients with lower KM values tend to experience larger shifts in plasma concentrations during dosage adjustments. They also exhibit a more significant change in the rate of drug elimination compared to those with higher KM values. This variability in KM values underscores the importance of personalized medicine and dosage adjustments.
From Chapter 8:
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