Translational PK/PD modeling for cardiovascular safety assessment of drug candidates: Methods and examples in drug development

Authors: Caruso A, Frances N, Meille C, Greiter-Wilke A, Hillebrecht A, Lavé T
Publication: J Pharmacol Toxicol Methods
Keywords: cardiovascular safety pharmacology, nonlinear mixed effects modeling, PK/PD modeling, telemetry studies, translation to human
Software: GastroPlus®

Introduction

Cardiovascular toxicity is a significant cause of candidate failure in drug development. Pharmacokinetic/pharmacodynamic (PK/PD) modeling may reduce attrition by improving the understanding of the relationship between drug exposure and changes in cardiovascular endpoints. Diverse examples are discussed that elucidate how modeling can facilitate the interpretation of cardiovascularsafety data in animals and enable quantitative translation of preclinical findings to man.