PBPK Modeling as an Alternative Method of Interspecies Extrapolation that Reduces the Use of Animals: A Systematic Review

Introduction: Physiologically based pharmacokinetic (PBPK) modeling is a computational approach that simulates the anatomical structure of the studied species and presents the organs and tissues as compartments interconnected by arterial and venous blood flows. Aim: The aim of this systematic review was to analyze the published articles focused on the development of PBPK models for interspecies extrapolation in the disposition of drugs and health risk assessment, presenting to this modeling an alternative to reduce the use of animals. Methods: For this purpose, a systematic search was performed in PubMed using the following search terms: “PBPK” and “Interspecies extrapolation”. The revision was performed according to PRISMA guidelines. Results: In the analysis of the articles, it was found that rats and mice are the most commonly used animal models in the PBPK models; however, most of the physiological and physicochemical information used in the reviewed studies were obtained from previous publications. Additionally, most of the PBPK models were developed to extrapolate pharmacokinetic parameters to humans and the main application of the models was for toxicity testing. Conclusion: PBPK modeling is an alternative that allows the integration of in vitro and in silico data as well as parameters reported in the literature to predict the pharmacokinetics of chemical substances, reducing in large quantity the use of animals that are required in traditional studies.