10/11/2023
A tutorial for model-based evaluation and translation of cardiovascular safety in preclinical trials was developed to provide a comprehensive workflow for the nonclinical analysis of drug-induced effects on hemodynamic parameters. The proposed framework represents a sequential approach, including animal pharmacokinetic model development, modeling of the circadian variations and handling effects, parametrization of the safety effect, and animal-to-human translation. The tutorial highlights the most typical challenges associated with the data and proposes respected solutions, complemented with a reproducible example in R and Monolix software. The work is aimed at helping researchers conduct model-based analyses of the CV safety in animals with subsequent translation of the effect to humans seamlessly and efficiently.
