Title:PBPK Modeling as an Alternative Method of Interspecies Extrapolation
that Reduces the Use of Animals: A Systematic Review
Volume: 31
Issue: 1
关键词:
生理学,药代动力学,建模,外推,解剖结构,种间外推。
摘要:
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.
