治疗性抗体药物的药代动力学研究的思考  

Thinking on Pharmacokinetic Studies of Therapeutic Antibody Drugs

作　　者：刘昌孝[1] 蔡永明[1] 樊慧蓉[1] 

机构地区：[1]天津药物研究院释药技术与药代动力学国家重点实验室,天津新药安全性评价研究中心,天津300193

出　　处：《中国药学杂志》2014年第4期257-264,共8页Chinese Pharmaceutical Journal

摘　　要：抗体药物经历了近30年的发展历史,目前已有多种治疗性抗体药物成功地应用于临床,在临床前和临床的药代动力学研究也获得一定进展。本文从抗体药物药代动力学研究的挑战,抗体药物药代动力学研究的特点、药代动力学-药效动力学研究和抗体药物的药代动力学研究实例等四方面思考治疗性抗体药物的药代动力学研究问题。展望今后发展,其一是生物分析方法的建立面临挑战,也是保证研究结果的可靠性的基础。其二是药代动力学和药代动力学/药效动力学分析面临挑战。对于具有明显的靶向性抗体药物,靶向分布是药动学研究的关键,药代动力学/药效动力学模型数据分析、暴露量-效应评价,靶向递药释药的挑战更为突出。Antibody drugs have experienced development for nearly 30 years. There are varieties of therapeutic antibody drugs suc- cessfully used in clinical practice. The design of pre-elinical and clinical pharmacokinetic studies for antibody drugs has achieved some progress. This article analyzed the issues in the pharmacokinetic studies of therapeutic antibody drugs from four aspects, including challenges for pharmaeokinetic studies, pharmacokinetic characteristics, pharmacokinetic-pharmaeodynamic research and some exam- ples of pharmaeokinetic studies. As for the prospects for future development, one of challenges is the establishment of bio-analytiea] methods, which ensure the reliability of the basic findings. Another challenge is the PK and PK/PD analysis. For antibody drugs dis- playing obvious targeting ability, target distribution is the key point of their pharmaeokinetic studies. PK/PD model for data analysis, exposure-response assessment, and release of targeted drug delivery face more prominent challenges.

关 键 词：抗体药物 药代动力学 生物分析 靶向分布 药代动力学-药效动力学研究 研究挑战 

分 类 号：R917[医药卫生—药物分析学] Q813[医药卫生—药学]