利妥昔单抗药物个体化治疗的药学进展

Pharmaceutical progress in individualized rituximab treatment

利妥昔单抗是采用基因工程技术合成的人鼠嵌合单克隆抗体,通过特异性结合B细胞表面的跨膜蛋白CD20而发挥药理效应。利妥昔单抗临床治疗效果显著,但药理机制复杂,药代动力学/药效动力学(PK/PD)呈非线性且变异度很大,为临床应用的有效性和安全性带来较大的变异性和不确定性,需要实施个体化治疗来提高其用药合理性。目前,利妥昔单抗已具备治疗药物监测(TDM)的基本条件,如血药浓度检测技术、肿瘤生物标志物和相关基因多态性的检测技术等。利用这些技术,结合疾病诊断、人群特殊性、给药途径和药物相互作用等因素综合分析,可以构建利妥昔单抗PK/PD模型,对其疗效、毒性和耐药进行预测。药师参与利妥昔单抗的个体化治疗,开展TDM,具有重要意义,可为患者提供更安全有效的个体化治疗。

Rituximab is a human‑mouse chimeric monoclonal antibody synthesized using genetic engineering technology and exert pharmacological effects by specifically binding to the transmembrane protein CD20 on the surface of B cells.The clinical therapeutic effect of rituximab is significant,but its phar‑macological mechanism is complex,the pharmacokinetics/pharmacodynamics(PK/PD)presents as nonlinear models and is highly variable,which brings great variability and uncertainty to the effectiveness and safety of rituximab in clinic,so individualized therapy needs to be implemented to improve the rationality of medica‑tion.At present,rituximab has the basic conditions for therapeutic drug monitoring(TDM),such as detection technology of blood drug concentration,tumor biomarkers,and related genetic polymorphisms.Using these technologies,combined with comprehensive analysis of factors such as disease diagnosis,population specificity,route of administration,and drug interactions,the PK/PD model of rituximab can be constructed to predict the efficacy,toxicity,and drug resistance.It is of great significance for pharmacists to participate in the indi‑vidualized rituximab treatment and carry out TDM,which can provide safer and more effective individualized treatment for patients.