Iwasaki Kazuhide, Uno Yasuhiro, Utoh Masahiro, Yamazaki Hiroshi
Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., 2-1-1 Fushimi-machi, Chuo-ku, Osaka 541-0044, Japan.
Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., 16-1 Minami Akasaka, Kainan, Wakayama 642-0017, Japan.
Drug Metab Pharmacokinet. 2019 Feb;34(1):55-63. doi: 10.1016/j.dmpk.2018.02.003. Epub 2018 Mar 20.
Animal species used in the preclinical studies for development of monoclonal antibody (mAb) drugs are surveyed in this review. Relevant animal species for preclinical studies of mAb candidates are those express desired epitope of mAb candidates. Cynomolgus monkeys cross-react with mAb drugs much higher than other animal species commonly used in preclinical studies such as absorption, distribution, metabolism and excretion (ADME), efficacy, and toxicity studies, for development of new drugs. Moreover, plasma exposure of the mAb drugs in humans is predicted well from the exposure in the monkeys, and the placental transfer of immunoglobulin G (IgG, all the mAb drugs contain IgG) from mother to fetus is similar between humans and the monkeys from a viewpoint of time course and plasma level of IgG transferred. These observed findings indicate that the monkeys are the most suitable animal species used in the ADME and toxicity studies for development of new mAb drugs.
本综述对用于单克隆抗体（mAb）药物研发的临床前研究的动物物种进行了调查。用于mAb候选药物临床前研究的相关动物物种是那些表达mAb候选药物所需表位的物种。食蟹猴与mAb药物的交叉反应比临床前研究中常用的其他动物物种（如新药研发中的吸收、分布、代谢和排泄（ADME）、疗效和毒性研究）要高得多。此外，从猴子体内的暴露情况可以很好地预测mAb药物在人体中的血浆暴露情况，并且从IgG转移的时间进程和血浆水平来看，人类和猴子之间从母亲到胎儿的免疫球蛋白G（IgG，所有mAb药物都含有IgG）的胎盘转移情况相似。这些观察结果表明，猴子是用于新mAb药物研发的ADME和毒性研究中最合适的动物物种。
