de Sousa G, Florence N, Vallès B, Coassolo P, Rahmani R
INSERM/Centre de Recherches INRA, Antibes, France.
Cell Biol Toxicol. 1995 Aug;11(3-4):147-53. doi: 10.1007/BF00756516.
Given the crucial role played by hepatocytes in the detoxification/toxification processes of drugs, these cells have been increasingly used during the last decade in various pharmaco-toxicological areas. The majority of these studies have, however, dealt with animal cells, although examples of failures in the extrapolation of the data to man are frequent. This drawback, together with the ethical considerations in performing in vivo experiments, makes the application of the human hepatocyte model critical in the preclinical evaluation of new compounds. However, before making extensive use of these promising tools for prospective pharmaceutical research, one must ensure that they can generate data that correlate well with those obtained in vivo. This is only possible through extensive studies on drugs showing a variety of phase I and phase II metabolic pathways in hepatocytes from different species, including man, and comparison with in vivo data. Providing this validation step is undertaken, the use of such systems in drug research and development may greatly enhance the rational design of safe and effective drugs, allowing savings in time, cost and test materials as well as minimizing the use of animals.
鉴于肝细胞在药物解毒/毒化过程中发挥的关键作用，在过去十年中，这些细胞在各个药物毒理学领域的应用越来越广泛。然而，这些研究大多涉及动物细胞，尽管将数据外推至人体时失败的例子屡见不鲜。这一缺陷，再加上进行体内实验时的伦理考量，使得人类肝细胞模型在新化合物的临床前评估中至关重要。然而，在广泛使用这些有前景的工具进行前瞻性药物研究之前，必须确保它们能够生成与体内获得的数据高度相关的数据。这只有通过对在包括人类在内的不同物种的肝细胞中显示出各种I期和II期代谢途径的药物进行广泛研究，并与体内数据进行比较才能实现。如果进行了这一验证步骤，那么在药物研发中使用此类系统可能会极大地促进安全有效药物的合理设计，节省时间、成本和测试材料，并尽量减少动物的使用。
