Sekino Clinical Pharmacology Clinic, Tokyo, Japan.
Invest New Drugs. 2009 Dec;27(6):579-82. doi: 10.1007/s10637-009-9223-y. Epub 2009 Feb 10.
Heparinized human whole blood from 16 adult volunteers was stimulated with achievable blood concentrations of trastuzumab and rituximab at 37 degrees C for 4 h, then CCL20, IL8, and beta-actin mRNA were quantified. The fold increase of beta-actin was all less than 1.5, and heat aggregated IgG induced both IL8 and CCL20 mRNA in all cases, suggesting that the assay was performed appropriately. Rituximab reduced the levels of CCL20 mRNA in approximately 1/3 of subjects, whereas 50 μg/ml trastuzumab induced IL8 and CCL20 mRNA in more than half of subjects. Although the results do not directly indicate the toxicity of antibody medicines, the individual variation found under physiological ex vivo condition will be an interesting clinical research model for drug safety analysis.
用可达血药浓度的曲妥珠单抗和利妥昔单抗在 37°C 刺激 16 位成人志愿者的肝素化全血 4 小时，然后定量 CCL20、IL8 和β-肌动蛋白 mRNA。β-肌动蛋白的倍数增加均小于 1.5，并且在所有情况下，热聚集 IgG 均诱导 IL8 和 CCL20 mRNA，表明该测定方法是适当的。利妥昔单抗使大约 1/3 的受试者的 CCL20 mRNA 水平降低，而 50μg/ml 的曲妥珠单抗使超过一半的受试者的 IL8 和 CCL20 mRNA 诱导。尽管这些结果并不直接表明抗体药物的毒性，但在生理的离体条件下发现的个体差异将是药物安全性分析的一个有趣的临床研究模型。
