Target mediated drug disposition – a population PKPD analysis of literature data

In this second webinar, the authors continue presenting new material planned for a future edition of PK/PD Data Analysis, focusing on a target-mediated drug disposition (TMDD) case study. The session emphasizes that, for TMDD systems, in vivo potency (IC₅₀) reflects not only binding affinity but also target turnover and complex kinetics, and therefore should not be replaced by simple dissociation constants (K_d) when predicting efficacious concentrations or doses.

Using published clinical data from a single–IV-infusion monoclonal antibody study with multiple dose groups and controls, the authors simulate a population dataset for repeated dosing. The simulated regimen includes four doses administered over time, with between-subject variability incorporated based on reported parameter uncertainty. The webinar demonstrates how to analyze these data using a TMDD population model in Phoenix to predict steady-state concentrations and key pharmacodynamic parameters such as IC₅₀, highlighting the importance of understanding target biology in dose selection