Surgical and pharmacological animal models used in drug metabolism and pharmacokinetics

Abstract

1. Mechanistic approaches in drug metabolism and pharmacokinetics during drug discovery depend upon animal models to increase the understanding of the absorption and disposition of new compounds. These animal models are also important to understand the complex interplay of biochemical and physiological events, and for the ability to answer questions in a reasonable time frame while interrogating numerous chemical structures. Many animal models have been described for understanding absorption, distribution, metabolism, and excretion and this review attempts to summarise some of these models.

2. The focus is primarily on surgical and pharmacological models for pharmacokinetic studies in rodents with special emphasis on descriptive methodologies for researchers embarking on in vivo studies. In this review, the surgical approaches include the mechanical instrumentation of anatomical structures, e.g. abdominal cavity, marginal ear vein, while pharmacological models are restricted to chemical inhibition of the cytochrome P450 enzymes and P-gp to understand hepatic metabolism or brain penetration and intestinal absorption, respectively.

3. The purpose of this review is not to exhaustively characterise each model but to serve as a general resource for investigators interested in performing these models.

Keywords::

• Animal model
• pharmacokinetics
• ADME
• drug discovery

Acknowledgements

The authors would like to thank Ms Aude Weigel and Dr Jerome Segrestaa for their helpful contributions to the in vivo animal work and in vitro experiments, respectively. Also, a special thank you to Dr Chris Kohl for the many helpful discussions on a variety of topics related to DMPK and drug discovery.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.