This is the first in a series of five models used to illustrate different types of pharmacokinetic-based drug-drug interactions (DDI). The model demonstrates the characteristics of time dependent inhibition (TDI) or mechanism based enzyme inhibition. It demonstrates how the inhibitor’s potency parameter, KI (concentration that results in half-maximal inhibition) and the inhibitor’s parameter representing its destructive power, kinact (the maximal rate constant of inactivation) impact the extent of inhibition. It also demonstrates the relationship between kobs and kinact . Finally the model shows how the enzyme’s degradation rate constant controls recovery from a TDI.
Link to Model
See Appendix E: Enzyme Kinetics: Michaelis Menten Equation and Models for Inhibitors and Inducers of Drug Metabolism
Topics relevant to this model are covered in the following sections:
– E.2.2 Time-Dependent Inhibition
– E.2.2.1 Mathematical Model for the Effect of TDI on Enzyme Kinetics
– E.2.2.2 Understanding the Parameters of of TDI though Simulation
Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook and Computer Simulations 2nd Edition
By: Sara E. Rosenbaum
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