BACKGROUND The anti-CD20 antibody rituximab, which promotes the selective depletion of CD20 positive B cells, was the first targeted therapy that was approved for the treatment of B-cell malignancies, and it is now widely prescribed in both malignant and non-malignant, immune-related diseases. However, the cause of its various clinical responses in certain diseases, have not been clearly elucidated. The variabilities in inter-individual pharmacokinetic and the emerging evidence of the relationships between pharmacokinetic and pharmacodynamic may provide a better understanding of this drug. METHODS We searched and summarized the latest published articles on rituximab pharmacokinetic profiles and the pharmacokinetic/pharmacodynamic models in different patient populations, including B-cell malignancies, rheumatoid arthritis, ANCA-associated vasculitis, and glomerular kidney diseases. RESULTS Most pharmacokinetic data are drawn from clinical studies in oncology clinical practice. Body weight, gender, and antigen-related factors are proven to be the key factors affecting rituximab pharmacokinetics. In addition, the positive exposure-response relations were reported, which provide encouraging evidence for individualized therapies. While in immune disorders, especially in the off-labeled indications, pharmacokinetic studies are quite limited. Compared with that in B-cell malignancies, the differences in the pharmacokinetic parameters may be attributed to the different pathogeneses of diseases, mechanisms of action and dosing strategies. However, the correlation between drug exposure and clinical outcomes remains unclear. CONCLUSION Here, we provide an overview of the complexities associated with rituximab pharmacokinetics and pharmacodynamics in different diseases. Although many influencing factors need to be verified in future studies, a better understanding of the relationships between pharmacokinetic and pharmacodynamic may assist in optimizing rituximab clinical practice.

中文翻译：

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不同疾病状态对利妥昔单抗药代动力学的影响。

背景 抗CD20抗体利妥昔单抗可促进CD20阳性B细胞的选择性清除，是首个获批用于治疗B细胞恶性肿瘤的靶向疗法，目前广泛用于恶性和非恶性、免疫相关疾病。然而，其在某些疾病中的各种临床反应的原因尚未明确阐明。个体间药代动力学的变异性和新出现的药代动力学和药效学之间关系的证据可能有助于更好地了解这种药物。方法 我们检索并总结了最新发表的关于利妥昔单抗药代动力学特征和不同患者群体的药代动力学/药效学模型的文章，包括 B 细胞恶性肿瘤、类风湿性关节炎、ANCA 相关的血管炎和肾小球肾病。结果 大多数药代动力学数据来自肿瘤临床实践中的临床研究。体重、性别和抗原相关因素被证明是影响利妥昔单抗药代动力学的关键因素。此外，报告了积极的暴露-反应关系，这为个体化治疗提供了令人鼓舞的证据。而在免疫疾病中，尤其是在标示外的适应症中，药代动力学研究非常有限。与 B 细胞恶性肿瘤相比，药代动力学参数的差异可能归因于疾病的发病机制、作用机制和给药策略的不同。然而，药物暴露与临床结果之间的相关性仍不清楚。结论在这里，我们概述了与利妥昔单抗在不同疾病中的药代动力学和药效学相关的复杂性。尽管在未来的研究中需要验证许多影响因素，但更好地了解药代动力学和药效学之间的关系可能有助于优化利妥昔单抗的临床实践。