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8.3 : Nonlinear Pharmacokinetics: Michaelis-Menten Equation

The Michaelis–Menten equation is a fundamental model for describing capacity-limited kinetics in drug metabolism. It offers insights into the rate of decline of plasma drug concentration Cp over time, with Vmax and KM as pivotal parameters.

Vmax represents the maximum achievable process rate, while KM, known as the Michaelis constant, signifies the drug concentration at which the process rate reaches half its maximum. This relationship between Vmax, KM, and Cp gives rise to three distinct scenarios that shed light on the dynamics of drug metabolism.

First, when KM = Cp, the process rate operates at half its maximum capacity. Conversely, if KM > Cp, the process rate mirrors first-order elimination, a pattern typically observed in most drugs at therapeutic levels. On the other hand, when KM < Cp, the process maintains a constant rate akin to zero-order elimination. Certain drugs, such as salicylates and phenytoin, follow first-order kinetics at lower therapeutic doses. In this state, the rate of drug elimination is proportional to the drug concentration. However, when these drugs are administered at elevated therapeutic doses, their metabolism saturates the hepatic mixed-function oxidases. This saturation shifts the kinetics to a zero-order pattern, where the elimination rate becomes constant and independent of drug concentration. The graphical representation of the Michaelis–Menten equation, known as the Michaelis–Menten plot, illustrates an initial linear rate increase with concentration, transitioning to mixed-order kinetics at higher concentrations and ultimately culminating in a plateau at Vmax.

In summary, the Michaelis–Menten equation serves as a foundational tool for understanding the intricacies of capacity-limited drug metabolism. It delineates the interplay between Vmax, KM, and Cp in shaping the rate of drug elimination within the body.

Tags

Nonlinear PharmacokineticsMichaelis Menten EquationDrug MetabolismVmaxMichaelis ConstantKMPlasma Drug ConcentrationFirst order EliminationZero order EliminationHepatic Mixed function OxidasesRate Of Drug EliminationMichaelis Menten PlotCapacity limited Kinetics

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