Advantages, disadvantages and applications of in vitro hepatic metabolic models

Abstract

Abstract: The liver is the predominant organ participating metabolism of xenobiotics.Generally, drugs will be mainly eliminated from the body by the way of metabolism.Drug biotransformation is one of the most important events that affect the overall pharmacologic and toxic profile and the subsequent therapeutic and safety index.Hence, hepatic metabolism research is a key step in the preclinical drug discovery and development process.For this purpose, in vitro approaches using various hepatic metabolism models, with the merits of rapidness, accuracy, high throughput have been gaining increasing popularity in the academic and pharmaceutical fields.The presently used in vitro models includes recombinant enzymes, microsomes, cytosol, S9 fraction, cell lines, transgenic cell lines, primary hepatocytes, stem cell derived hepatic cell, precise liver slices and perfused liver.This review will describe the advantages, disadvantages and the applications of these in vitro models with the purpose of facilitating researchers to choose appropriate models to make reasonable evaluation of in vitro metablism and study the possible drug biotransformation model in liver,and finally to predict drug elimination mode in vivo scientifically.

Key words: In vitro hepatic metabolic model, Advantage and disadvantage, Application, Drug biotransformation

CLC Number:

R969.1

LI Dan, HAN Yong-long, YU Tao, MENG Xiang-le, YU Qi, WANG Jun, GUO Cheng. Advantages, disadvantages and applications of in vitro hepatic metabolic models[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(6): 688-694.

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