胃恶性肿瘤患者阿帕替尼的治疗药物监测研究

Study on the Therapeutic Drug Monitoring of Apatinib in Gastric Cancer Patients

目的:探讨在胃恶性肿瘤患者中开展阿帕替尼治疗药物监测的情况,为临床安全合理用药提供参考。方法:采用LC-MS/MS测定2021年1月~2023年3月期间我院胃恶性肿瘤患者体内阿帕替尼的暴露水平,分析药物浓度与不良反应,疗效及不同联合用药种类之间的关系,考察性别、年龄、联合用药及肝肾功能等因素对稳态谷浓度的影响。结果:阿帕替尼回归直线方程为Y=0.06512X+0.02745,r^(2)=0.9987,血清样本在1.00~500μg·L^(-1)内具有良好的线性,定量下限为1.00μg·L^(-1)。50例患者中,血清药物谷浓度范围为10.39~364.74μg·L^(-1),未发现疾病状况及不良反应与药物稳态谷浓度存在显著关联。与单抗类药物联用的阿帕替尼患者血药浓度显著高于紫杉醇组(P<0.05),其他各组之间差异无统计学意义(P>0.05)。肾小球滤过率(eGFR)是影响稳态谷浓度的重要因素。结论:在阿帕替尼治疗过程中,利用稳态谷浓度进行治疗药物监测的意义有限。阿帕替尼治疗期间需要密切关注肾功能的监测,并且在与不同化疗药物联合应用时,阿帕替尼代谢表现出显著的差异。

Objective:To investigate therapeutic drug monitoring of apatinib in patients with gastric malignancies,providing a reference for safe and rational clinical medication.Methods:Employing LC-MS/MS,we measured the exposure levels of apatinib in gastric malignancy patients at our institution from January 2021 to March 2023,analyzed the relationship between drug concentrations and adverse reactions,efficacy,and various combined drug types,and examined the impact of gender,age,combined medication,and liver and kidney functions on steady-state trough concentrations.Results:The regression equation for apatinib was Y=0.06512X+0.02745 and r^(2)=0.9987,demonstrating good linearity in serum samples within the 1.00-500μg·L^(-1) range and a lower limit of quantification of 1.00μg·L^(-1).Among the 50 patients studied,serum drug trough concentrations ranged from 10.39 to 364.74μg·L^(-1),with no significant correlation identified between disease status or adverse reactions and drug steady-state trough concentrations.Patients using apatinib in combination with monoclonal antibody drugs exhibited significantly higher blood drug concentrations than those in the paclitaxel group(P<0.05),with no significant differences observed among other groups.The estimated glomerular filtration rate(eGFR)was identified as a crucial factor affecting steady-state trough concentrations.Conclusion:The utility of steady-state trough concentrations for therapeutic drug monitoring during apatinib administration is limited.Attentive monitoring of renal function is requisite during apatinib treatment,and significant metabolic variations of apatinib are observed when combined with different chemotherapy drugs.