In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part III.

ABSTRACT: The development of in vitro/in vivo translational methods and a clinical trial framework for synergistically acting drug combinations are needed to identify optimal therapeutic conditions with the most effective therapeutic strategies. We performed physiologically based pharmacokinetic-pharmacodynamic (PBPK/PD) modelling and virtual clinical trial simulations for siremadlin, trametinib, and their combination in a virtual representation of melanoma patients. In this study, we built PBPK/PD models based on data from in vitro absorption, distribution, metabolism, and excretion (ADME), and in vivo animals' pharmacokinetic-pharmacodynamic (PK/PD) and clinical data determined from the literature or estimated by the Simcyp simulator (version V21). The developed PBPK/PD models account for interact

SUBMITTER: Witkowski J 

PROVIDER: S-EPMC9917191 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature