大剂量甲氨蝶呤治疗淋巴瘤的血药浓度和不良反应影响因素分析

Analysis of influential factors for blood concentrations and adverse drug reaction in the treatment of lymphoma with high-dose methotrexate

目的探讨应用大剂量甲氨蝶呤(HD-MTX)治疗淋巴瘤时,影响HD-MTX血药浓度和不良反应的因素。方法采用回顾性分析的方法,收集2020年7月至2021年11月广东药科大学附属第一医院所有进行了HD-MTX血药浓度监测的患者信息,包括患者的病历号、年龄、性别、身高、体质量、化疗方案、给药剂量,以及给药前后丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素、肌酐清除率(CrCl)、白蛋白(ALB)等检验指标,记录不同时间HD-MTX的血药浓度(c6 h、c24 h、c48 h)检测值,提取合并使用质子泵抑制剂(PPIs)类药物信息,并评估用药后48 h内发生的所有不良反应。采用单因素方差分析、多元线性回归、χ^(2)检验进行影响因素分析。结果本研究共纳入133例患者,HD-MTX治疗淋巴瘤时血药浓度单因素分析结果显示,年龄、CrCl对c6 h有影响(P<0.05),年龄、CrCl、ALB对c24 h有影响(P<0.05),年龄、体质量指数(BMI)、CrCl、合并使用PPIs、ALB对c48 h有影响(P<0.05)。多元线性回归分析结果显示,年龄、CrCl对c6 h无影响(P>0.05),年龄是c24 h的主要影响因素(P<0.05),CrCl、合并使用PPIs是c48 h的主要影响因素(P<0.05),方差膨胀系数均在1~3.5之间,表明分析结果均可接受。总体不良反应发生率为51.13%,其中血液和淋巴系统反应最常见。影响因素结果显示,年龄、BMI、肝功能、CrCl对不良反应发生率有影响(P<0.05)。结论在HD-MTX治疗淋巴瘤的过程中,需考虑患者年龄、CrCl及合并使用PPIs情况,做好患者血药浓度监测;同时,患者年龄、BMI、肝功能和CrCl对不良反应发生率有影响。

OBJECTIVE To discuss the factors affecting the blood concentration of high-dose methotrexate(HD-MTX)and the occurrence of adverse drug reactions(ADR)when treating lymphoma with HD-MTX.METHODS From July 2020 to November 2021,the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis,such as medical record number,age,sex,height,body mass,chemotherapy plan,dosage;test indexes such as alanine transaminase,aspartate transaminase,total bilirubin,creatinine clearance(CrCl),albumin(ALB)and other indexes were also collected before and after administration.The blood concentrations(c6 h,c24 h,c48 h)of HD-MTX were recorded,drug information of proton pump inhibitors(PPIs)was extracted and used,and ADR occurring within 48 h after administration were all evaluated.Single factor analysis,multiple linear regression andχ^(2) test were used to analyze the influential factors.RESULTS A total of 133 patients were included in this paper.The results of the single factor analysis of HD-MTX blood drug concentration showed that age,CrCl had an effect on c 6 h(P<0.05);age,CrCl and ALB had an effect on c24 h(P<0.05);age,body mass index(BMI),CrCl,combined use of PPIs and ALB had an effect on c48 h(P<0.05).The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h(P>0.05),age was the main influential factor of c 24 h(P<0.05),and CrCl and combined use of PPIs were the main influential factors of c48 h(P<0.05);the coefficient of variance expansion was between 1 and 3.5,indicating that the analysis results were acceptable.The overall incidence of adverse reactions was 51.13%,of which the blood and lymphatic system reactions were the most common.The results of the influential factors of ADR showed that age,BMI,liver function and CrCl had effect on the incidence of ADR(P<0.05).CONCLUSIONS During the process of HD-MTX in the treatment of lymphoma,the patient’s age,CrCl and combined use of PPIs should be considered,and the patient’s blood concentration should be monitored;at the same time,the age of patients,BMI,liver function and CrCl have an impact on the incidence of ADR.