34例骨肉瘤患者大剂量甲氨蝶呤化疗后血药浓度与不良反应分析  

Analysis of plasma concentration of methotrexate and adverse reactions in 34 patients with osteosarcoma

作　　者：赵晨 兰云意 杨柱梅[1] 史筱倩[1] 周永春 孔树佳[1] ZHAO Chen;LAN Yunyi;YANG Zhumei;SHI Xiaoqian;ZHOU Yongchun;KONG Shujia(Department of Pharmacy,Yunnan Cancer Hospital,Kunming,Yunnan,650118,China;Molecular Diagnostic Center,Yunnan Cancer Center,Kunming,Yunnan,650118,China)

机构地区：[1]云南省肿瘤医院药学部,云南昆明650118 [2]云南省癌症中心分子诊断分中心,云南昆明650118

出　　处：《肿瘤药学》2022年第1期77-81,共5页Anti-Tumor Pharmacy

摘　　要：目的分析骨肉瘤患者使用大剂量甲氨蝶呤(HD-MTX)化疗后肝功能损伤和骨髓抑制的发生情况,探讨肝损伤和骨髓抑制的发生与MTX血药浓度的相关性。方法选取我院2019年1月—12月使用HD-MTX治疗的34例骨肉瘤患者,采用HPLC法测定MTX静脉滴注开始后24 h、48 h、72 h的血药浓度(C_(24h)、C_(48h)、C_(72h)),同时测定患者化疗后肝功能和血常规,采用Pearson法分析药物性肝损伤和骨髓抑制的发生与不同时间点MTX血药浓度的相关性。结果 HD-MTX化疗完成后,16例患者(47.06%)出现急性药物性肝损伤,主要表现为GPT升高;19例患者(55.88%)出现骨髓抑制,主要表现为WBC和NE下降。GPT升高与MTX血药浓度无明显相关性(P>0.05),而WBC和NE下降与24 h、48 h的MTX血药浓度显著相关(P<0.01)。结论 HD-MTX所致药物性肝损伤的发生与MTX血药浓度无明显相关性,但骨髓抑制的发生与MTX血药浓度显著相关,给药后24 h和48 h的MTX血药浓度越高,患者越易发生骨髓抑制。Objective To analyze the occurrence of liver injury and bone marrow suppression after high-dose methotrexate (HD-MTX) chemotherapy in patients with osteosarcoma,and to explore the correlation between the adverse reactions and MTX blood concentration.Methods Thirty-four patients with osteosarcoma treated with HD-MTX were selected in this study.The plasma concentration of MTX was detected by HPLC method at 24 h,48 h and 72 h after the beginning of MTX infusion.The liver function and blood routine indexes were also measured.Pearson method was used to analyze the correlation between the adverse reactions and the concentration of MTX at different time points.Results After HD-MTX chemotherapy,16 patients (47.06%) developed acute drug-induced liver injury,mainly with elevated GPT;19 patients(55.88%) developed bone marrow suppression,mainly with decreased WBC and NE.There was no correlation between the increase of GPT and the MTX blood concentration (P>0.05).However,the decrease of WBC and NE were significantly related to the 24 h and 48 h MTX blood concentration (P<0.01).Conclusion The study reveals the acute drug-induced liver injury caused by HD-MTX is not related to the MTX plasma concentrations at different time points.However,the bone marrow suppression caused by HD-MTX is significantly related to the MTX plasma concentration.The higher the MTX 24 h and 48 h blood concentration is,the more likely the bone marrow suppression will occur.

关 键 词：大剂量 甲氨蝶呤 骨肉瘤 血药浓度 不良反应 

分 类 号：R738.1[医药卫生—肿瘤]