Some drugs act by binding covalently to their receptors. As a result, the target is destroyed and its function returns only when it has been replaced by newly synthesized product. The target may be a protein, DNA, an enzyme, or a cell at any stage of development. This model has been applied to the action of the proton pump inhibiotrs, which bind to and destroy the H+,K+-ATPase pumps in the parietal cells of the gastric mucosa. Normal proton secretion is restored only when the pumps are replaced by newly synthesized functioning pumps (i.e., the usual turnover time of the system).
Link to Model
See Chapter 20: Semimechanistic PK-PD Models
Topics relevant to this model are covered in the following sections:
– 20.7 Irreversible Drug Effects
– 20.7.1 Application of the Turnover Model to Irreversible Drug Action
– 20.7.1.1 Simulation Exercise
Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook and Computer Simulations 2nd Edition
By: Sara E. Rosenbaum
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