阿达木单抗生物类似药HS016与阿达木单抗（修美乐®）在健康受试者和强直性脊柱炎患者中的药代动力学参数比较评估：群体药代动力学建模
Comparative assessment of pharmacokinetic parameters between HS016, an adalimumab biosimilar, and adalimumab (Humira®) in healthy subjects and ankylosing spondylitis patients: Population pharmacokinetic modeling.
作者信息
Zeng Xiaofeng, Zhang Jing, Yu Jicheng, Wu Xiaojie, Chen Yuancheng, Wu Jufang, Yang Xiaoli, Wang Jingjing, Cao Guoying
机构信息
Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
Phase I Clinical Trial Center, Huashan Hospital, Fudan University, Shanghai, China.
出版信息
Adv Clin Exp Med. 2022 May;31(5):499-509. doi: 10.17219/acem/145947.
BACKGROUND
The HS016 is an adalimumab biosimilar related to the immunoglobulin G1 (IgG1) antibody, with a similar amino acid sequence.
OBJECTIVES
To quantify the differences in the pharmacokinetic (PK) parameters of HS016 and adalimumab in healthy individuals and patients with ankylosing spondylitis (AS).
MATERIAL AND METHODS
The PK data for HS016 and adalimumab were obtained in a randomized, double-blind, phase 1 clinical study in Chinese healthy subjects after a single-dose subcutaneous administration (136 healthy subjects), and in a randomized, double-blind, phase 3 trial of AS patients who received subcutaneous injection of HS016 or adalimumab once every 2 weeks for 24 weeks (366 AS patients).
RESULTS
The time course of HS016 and adalimumab was characterized by a one-compartment model with first-order absorption and elimination kinetics. Age, body weight, creatinine clearance (CLcr) and anti-drug antibody were covariates for the apparent clearance (CL/F); body weight and subject type were significant covariates for the apparent volume of distribution (V/F). The V/F and CL/F were estimated at 11.3 L and 0.0102 L/h. The ratios of the geometric least square (LS) means (HS016 compared to the adalimumab treatment group after multiple doses) in healthy subjects were 97.14 (87.70, 107.59) for the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and 99.14 (90.03, 109.16) for the maximum serum drug concentration within a steady-state dosing interval (Cmax, ss); the ratios (90% confidence interval (90% CI)) in AS patients were 97.03 [84.10; 111.96] for the AUC within the steady-state dose intervals (AUC0-tau) and 99.62 [88.09; 112.68] for Cmax, ss.
CONCLUSIONS
The systemic exposure of HS016 was similar to that of adalimumab in healthy subjects and AS patients, demonstrating PK similarity.
背景
HS016是一种与免疫球蛋白G1（IgG1）抗体相关的阿达木单抗生物类似药，具有相似的氨基酸序列。
目的
量化HS016和阿达木单抗在健康个体及强直性脊柱炎（AS）患者体内药代动力学（PK）参数的差异。
材料与方法
HS016和阿达木单抗的PK数据来自一项在中国健康受试者中进行的单剂量皮下给药的随机、双盲1期临床研究（136名健康受试者），以及一项针对AS患者的随机、双盲3期试验，这些患者每2周皮下注射一次HS016或阿达木单抗，共24周（366名AS患者）。
结果
HS016和阿达木单抗的血药浓度-时间过程符合一级吸收和消除动力学的单室模型。年龄、体重、肌酐清除率（CLcr）和抗药抗体是表观清除率（CL/F）的协变量；体重和受试者类型是表观分布容积（V/F）的显著协变量。V/F和CL/F分别估计为11.3 L和0.0102 L/h。在健康受试者中，从时间零点到最后可测量浓度的浓度-时间曲线（AUC0-t）的几何最小二乘（LS）均值之比（多次给药后HS016与阿达木单抗治疗组相比）为97.14（87.70，107.59），稳态给药间隔内的最大血清药物浓度（Cmax, ss）之比为99.14（90.03，109.16）；在AS患者中，稳态剂量间隔内的AUC（AUC0-tau）之比（90%置信区间（90%CI））为97.03 [84.10; 111.96]，Cmax, ss之比为99.62 [88.09; 112.68]。
结论
在健康受试者和AS患者中，HS016的全身暴露与阿达木单抗相似，表明PK相似。
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