重组抗肿瘤坏死因子-α人鼠嵌合单克隆抗体在类风湿关节炎患者体内药动学研究

Pharmacokinetics of anti-TNF rcMAb injection in Chinese patients with rheumatoid arthritis

目的:研究连续静脉滴注重组抗肿瘤坏死因子-α人鼠嵌合单克隆抗体(anti-TNF rcMAb)在类风湿关节炎患者体内的药动学。方法:按GCP指导原则设计试验方案,选择9例类风湿关节炎患者,年龄(41±16)岁,在2h内匀速静脉滴注anti-TNF rcMAb,每次3mg·kg-1,共给药5次,用酶联免疫吸附法(ELISA)测定人血清中各点anti-TNF rcMAb浓度。采用DAS2.1.1软件进行数据处理,计算药动学参数。结果:受试者多次静脉滴注anti-TNF rcMAb,按非房室模型计算,主要药动学参数t1/2为(9.2±1.8)d,Cssmax为(0.008±0.001)mg·L-1,Tssmax为(0.092±0.018)d,AUCss为(248±38)mg.d.L-1,Vss为(0.10±0.08)L·kg-1,DF为(5.5±0.6)。受试者在给药期间未出现严重不良反应。结论:本研究在给药后第3次时血药浓度可达到稳态,连续给药5次后体内未见蓄积,该方案适宜在临床推广使用。建议临床按此方案用药时,使用时间不宜过长,以减少药物不良反应。

Objective：To investigate the pharmacokinetics of anti-TNF rcMAb injection at multiple doses in Chinese patients with rheumatoid arthritis. Methods：The protocol was designed according to GCP principles. Nine patients with rheumatoid arthritis at age of （41±16）y were intravenously administered with 5 doses of 3 mg·kg^-1 anti-TNF rcMAb in 2 h. The plasma concentrations of anti-TNF rcMAb were determined by enzyme linked immunosorbent assay （ELISA）. The pharmacokinetic parameters were calculated using DAS 2.1.1 program. Results：The main pharmacokinetic parameters after multiple doses were calculated based on non-compartment model. The major pharmacokinetics parameters were as following：t1/2 was （9.2±1.8） d,Css max was （0.08±0.001） mg·L^-1,Tss max was （0.092±0.018） d,AUCss was （248±38） mg·d·L^-1,Vss was （0.10±0.08） L·kg^-1,DF was （5.5±0.6）. No serious adverse drug effects were observed during the whole period of the study. Conclusion：Effective concentration in vivo has been achieved after intravenous infusions of anti-TNF rcMAb after 3 times,and no accumulation in the body after 5 times. The recommended dosing schedule is that it should be administered for a short term for the clinical safety.