Department of Clinical Pharmacology, Genentech, Inc., South San Francisco, California, USA.
Quantitative Solutions Inc., Menlo Park, California, USA.
CPT Pharmacometrics Syst Pharmacol. 2023 Jun;12(6):795-807. doi: 10.1002/psp4.12953. Epub 2023 Mar 10.
The pharmacokinetic (PK) characteristics of omalizumab and its pharmacodynamic (PD) effect in patients has yet to be fully characterized in chronic spontaneous urticaria, which could elucidate its pathogenesis and treatment response. This study has two objectives; (1) characterize the population PK of omalizumab and its PD effect on IgE, and (2) develop a drug effect model of omalizumab in urticaria (via change in weekly itch severity score). The target-mediated population of PK/PD model incorporating omalizumab-IgE binding and turnover adequately described PK and PD of omalizumab. The effect compartment model and linear drug effect and additive placebo response adequately described placebo and treatment effects of omalizumab. Several baseline covariates were identified for PK/PD and drug effect models. The developed model has the potential to aid in understanding variability in PK/PD as well as response to omalizumab treatment.
奥马珠单抗的药代动力学（PK）特征及其在慢性自发性荨麻疹患者中的药效学（PD）效应尚未得到充分描述，这可能阐明其发病机制和治疗反应。本研究有两个目标；（1）描述奥马珠单抗的群体 PK 及其对 IgE 的 PD 效应，（2）通过每周瘙痒严重程度评分的变化，建立奥马珠单抗在荨麻疹中的药效学模型。纳入奥马珠单抗-IgE 结合和转化的靶向介导群体 PK/PD 模型充分描述了奥马珠单抗的 PK 和 PD。效应室模型和线性药物效应及附加安慰剂反应充分描述了奥马珠单抗的安慰剂和治疗效应。确定了几个与 PK/PD 和药物效应模型相关的基线协变量。所开发的模型有可能有助于了解 PK/PD 以及对奥马珠单抗治疗的反应的变异性。
