Advances in Preclinical Toxicology: Bridging In Vitro, In Vivo, and Translational Gaps

Abstract

Preclinical toxicology plays a pivotal role in drug development by assessing the safety profiles of therapeutic candidates before human trials. Recent advances in this field aim to bridge the translational gap between in vitro and in vivo models and clinical outcomes. Traditional animal models, though informative, often fail to fully predict human responses, prompting a shift towards more human-relevant systems. Innovations such as 3D cell cultures, organ-on-chip technologies, and high-throughput screening have revolutionized in vitro toxicology by offering improved physiological relevance and mechanistic insights. Concurrently, in vivo studies are increasingly integrating imaging modalities, biomarkers, and comics technologies to enhance sensitivity and early detection of toxicity. Moreover, translational toxicology emphasizes the alignment of preclinical findings with clinical data, using approaches like physiologically based pharmacokinetic (PBPK) modeling and systems biology to improve predictivity. These integrated strategies aim to reduce drug attrition, enhance patient safety, and streamline regulatory approval processes. This review provides a comprehensive overview of these advancements and highlights the ongoing need for collaborative, interdisciplinary efforts to refine and harmonize preclinical toxicology approaches for better clinical translation.