Population pharmacokinetics of cilengitide in adult and pediatric cancer patients from a nonlinear mixed-effects analysis

Cilengitide is an αvβ3/αvβ5‐integrin inhibitor investigated as an anticancer agent. This study aimed to develop a cilengitide population pharmacokinetic model using nonlinear mixed‐effects modeling of 136 adult patients with advanced solid tumors and to scale the pharmacokinetic parameters to the pediatric population. A stepwise approach was used, beginning with exploratory analyses checking database/target covariate relationships. A two‐compartment structural model was developed to describe cilengitide's concentration–time profile and assess covariates’ impact on pharmacokinetic parameters. A bootstrap procedure validated the base/final model stability. A two‐compartment model best described concentration–time data. Estimated structural model parameters were: 2.79 L h−1 m−2 central compartment mean systemic clearance, 6.75 L m−2 central compartment volume of distribution, 1.3 L h−1 m−2 intercompartmental clearance, and 3.85 L m−2 peripheral compartment volume of distribution. Mean half‐life was 0.9 and 3.8 h (α/β‐phase). Co‐medications and study populations had no impact, as the different studies were not significant model covariates. Weight and body surface area correlated with the pharmacokinetic parameters (r = 0.95, P