Deriving mechanism-based pharmacodynamic models by reducing quantitative systems pharmacology models: An application to warfarin.

ABSTRACT: Quantitative systems pharmacology (QSP) models integrate comprehensive qualitative and quantitative knowledge about pharmacologically relevant processes. We previously proposed a first approach to leverage the knowledge in QSP models to derive simpler, mechanism-based pharmacodynamic (PD) models. Their complexity, however, is typically still too large to be used in the population analysis of clinical data. Here, we extend the approach beyond state reduction to also include the simplification of reaction rates, elimination of reactions, and analytic solutions. We additionally ensure that the reduced model maintains a prespecified approximation quality not only for a reference individual but also for a diverse virtual population. We illustrate the extended approach for the warfarin effect on

SUBMITTER: Falkenhagen U 

PROVIDER: S-EPMC10088086 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature