Pharmacodynamic model of slow reversible binding and its applications in pharmacokinetic/pharmacodynamic modeling: review and tutorial.

ABSTRACT: Therapeutic responses of most drugs are initiated by the rate and degree of binding to their receptors or targets. The law of mass action describes the rate of drug-receptor complex association (k_on) and dissociation (k_off) where the ratio k_off/k_on is the equilibrium dissociation constant (K_d). Drugs with slow reversible binding (SRB) often demonstrate delayed onset and prolonged pharmacodynamic effects. This report reviews evidence for drugs with SRB features, describes previous pharmacokinetic/pharmacodynamic (PK/PD) modeling efforts of several such drugs, provides a tutorial on the mathematics and properties of SRB models, demonstrates applications of SRB models to additional compounds, and compares PK/PD fittings of SRB with other

SUBMITTER: Ren T 

PROVIDER: S-EPMC9578295 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature