Sign In

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.

From Chapter 8:

article

Now Playing

8.3 : Nonlinear Pharmacokinetics: Michaelis-Menten Equation

Nonlinear Pharmacokinetics

4 Views

article

8.1 : Nonlinear Pharmacokinetics: Overview

Nonlinear Pharmacokinetics

9 Views

article

8.2 : Nonlinear Pharmacokinetics: Causes of Nonlinearity

Nonlinear Pharmacokinetics

12 Views

article

8.4 : Determination of Michaelis Constant and Maximum Elimination Rate

Nonlinear Pharmacokinetics

9 Views

article

8.5 : Nonlinear Pharmacokinetics: Drug Elimination for IV Bolus Injection

Nonlinear Pharmacokinetics

4 Views

article

8.6 : Drug Distribution as One-Compartment Model and Elimination by Nonlinear Pharmacokinetics: Overview

Nonlinear Pharmacokinetics

5 Views

article

8.7 : Parameters Affecting Nonlinear Elimination: Zero-Order Input, First-Order Absorption and Two-Compartment Model

Nonlinear Pharmacokinetics

5 Views

article

8.8 : Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

Nonlinear Pharmacokinetics

4 Views

article

8.9 : Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response

Nonlinear Pharmacokinetics

8 Views

article

8.10 : Chronopharmacokinetics: Time-Dependent Pharmacokinetics

Nonlinear Pharmacokinetics

18 Views

article

8.11 : Nonlinear Pharmacokinetics: Bioavailability and Protein-Drug Binding

Nonlinear Pharmacokinetics

31 Views

article

8.12 : Nonlinear Pharmacokinetics: Role of Transporters

Nonlinear Pharmacokinetics

5 Views

JoVE Logo

Privacy

Terms of Use

Policies

Research

Education

ABOUT JoVE

Copyright © 2025 MyJoVE Corporation. All rights reserved