Ozoralizumab 是一种双特异性 NANOBODY® 化合物，可结合肿瘤坏死因子 α (TNFα) 和人血清白蛋白 (HSA)。 Ozoralizumab 抑制 TNFα 生理活性，同时由于其 HSA 结合能力而保持长期血浆保留。使用 II/III 期和 III 期试验中 494 名日本类风湿性关节炎 (RA) 患者的数据开发了群体药代动力学 (PK) 模型，以评估潜在 PK 协变量的影响。使用具有一级吸收和一级消除过程的单室模型描述了皮下给药后的 ozoralizumab PK。比例误差模型用于个体间和个体内变异性，并在表观清除率（CL/F）和表观分布体积（Vd/F）的个体间变异性之间设定协方差。体重、性别、抗药物抗体状态、估计肾小球滤过率和伴随的甲氨蝶呤使用被确定为 CL/F 的协变量，而体重和性别是最终模型中 Vd/F 的协变量。体重对 ozoralizumab 的 PK 影响最大，而其他协变量影响较小。当每 4 周给药 30 mg 时，体重 83.2 kg 的患者的预测稳态血浆谷浓度超过了维持 ozoralizumab 疗效所需的谷浓度，并且体重 42.5 kg 的患者的估计暴露量未超过平均暴露量80 mg，耐受良好的剂量，持续 52 周。我们开发了一个群体 PK 模型，该模型充分描述了日本 RA 患者中的 ozoralizumab PK，并且所评估的协变量均未显示出对 ozoralizumab PK 的临床相关影响。本文受版权保护。保留所有权利。本文受版权保护。版权所有。

Ozoralizumab is a bispecific NANOBODY® compound that binds tumor necrosis factor alpha (TNFα) and human serum albumin (HSA). Ozoralizumab inhibits the TNFα physiological activity while maintaining long-term plasma retention owing to its HSA-binding ability. A population pharmacokinetic (PK) model was developed using data from 494 Japanese patients with rheumatoid arthritis (RA) in phase II/III and phase III trials to assess the effects of potential PK covariates. The ozoralizumab PK after subcutaneous administration was described using a one-compartment model with first-order absorption and first-order elimination processes. A proportional error model was used for inter- and intra-individual variabilities, with covariance set between inter-individual variabilities of the apparent clearance (CL/F) and apparent distribution volume (Vd /F). Body weight, sex, anti-drug antibody status, estimated glomerular filtration rate, and concomitant methotrexate use were identified as covariates for CL/F, while body weight and sex were covariates for Vd /F in the final model. Body weight had the greatest effect on the PK of ozoralizumab, while the other covariates had minor effects. When administered at 30 mg every 4 weeks, the predicted steady-state plasma trough concentration in a patient weighing 83.2 kg exceeded the trough concentration required to maintain efficacy of ozoralizumab, and the estimated exposure in a patient weighing 42.5 kg did not exceed the mean exposure at 80 mg, a well-tolerated dose, throughout 52 weeks. We developed a population PK model that adequately described the ozoralizumab PK in Japanese patients with RA, and none of the evaluated covariates showed clinically relevant effects on the PK of ozoralizumab. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.