Horii I
Nippon Roche Research Center, Department of Preclinical Science, Kamakura City, Kanagawa Pref., Japan.
Toxicol Lett. 1998 Dec 28;102-103:657-64. doi: 10.1016/s0378-4274(98)00281-1.
Toxicokinetic (TK) study is generally required for toxicological evaluation and safety assessment, particularly in the pivotal toxicological studies which are requested on the basis of drug registration. The estimation points of TK data are: (1) determination of TK profile in toxicity study, (2) selection of dose, dosing form, alternative dosing route, (3) help for the evaluation of toxicity (non-effect/toxic dose, toxicological mechanism), (4) comparative evaluation between animal and human cases, (5) recommendation of the starting dose in the first human clinical trial. On the other hand, as a very recent trend, TK data are practically used for the purpose of drug discovery such as lead-optimization and candidate-selection. This paper presents practical examples of TK data in terms of their usefulness, and discusses how to evaluate the toxicity of a drug with the aid of a variety of TK studies.
毒代动力学（TK）研究通常是毒理学评价和安全性评估所必需的，特别是在基于药物注册要求开展的关键毒理学研究中。TK数据的估算要点包括：（1）在毒性研究中确定TK概况；（2）选择剂量、给药形式、替代给药途径；（3）辅助毒性评价（无作用/毒性剂量、毒理学机制）；（4）动物与人体病例的比较评价；（5）推荐首例人体临床试验的起始剂量。另一方面，作为一个最新趋势，TK数据实际上已用于药物研发目的，如先导化合物优化和候选药物选择。本文介绍了TK数据实用性方面的实际案例，并讨论了如何借助各种TK研究来评估药物的毒性。
