我国甲氨蝶呤血药浓度监测文献分析

Literature Analysis for the Current Status of Methotrexate Plasma Concentration Monitoring in China

目的:为制订甲氨蝶呤(MTX)个体化给药方案提供参考。方法:计算机检索Pub Med、中国期刊全文数据库、中文科技期刊数据库和万方数据库,纳入我国患者应用MTX并进行血药浓度监测的文献,统计分析患者病种、MTX监测例次、监测方法、监测时间点、甲酰四氢叶酸(CF)开始解救时间和停止解救标准、MTX参考浓度标准、文献发表时间和研究类型等信息。结果:共纳入146篇文献,合计6 109例患者,共计20 000余例次MTX血药浓度监测结果。其中,53篇文献为前瞻性研究,93篇为回顾性研究。结果表明,2005年1月-2009年12月发表了75篇MTX监测相关文献(占比51.4%);MTX血药浓度监测方法以荧光偏振免疫法(FPIA)和高效液相色谱法(HPLC)为主;43.5%的文献监测时间点为MTX用药后24、48、72和96 h,与美国食品药品管理局(FDA)推荐的相同;56.1%的文献采用FDA推荐的MTX参考浓度标准(24 h≤10μmol/L,48 h≤1μmol/L,72 h≤0.2μmol/L)。在急性淋巴细胞白血病(ALL)和非霍奇金淋巴瘤(NHL)中CF的开始解救时间普遍为MTX用药后36 h,而骨肉瘤的CF开始解救时间以用药后6 h和12 h为主;以MTX血药浓度<0.1μmol/L为CF停止解救标准的占73.6%,而以FDA推荐的MTX血药浓度<0.05μmol/L为停止解救标准的仅占8.3%。结论:目前我国对MTX的监测时间点、参考浓度标准、CF开始解救时间和停止解救标准等方面尚未完全统一,但趋于一致。建议相关机构根据中国人MTX的代谢特点,尽快建立国内MTX的血药浓度监测指南,以便更好地指导临床合理监测MTX血药浓度,进行个体化给药。

OBJECTIVE： To analysis the literature analysis of methotrexate （MTX） plasma concentration monitoring in China, and provide reference for developing MTX individual regimen. METHODS： Retrieved from PubMed, CJFD , VIP database and Wanfang database, literatures about patients using MTX for plasma concentration monitoring in China were enrolled, the diseases, monitoring numbers, monitoring methods and time points, rescue time and stop standard of leucovorin （CF）, reference concentra- tion standard, literature types and quality of patients were summarized. RESULTS： Totally 146 literature were included, involving 6 109 patients and 20 000 cases of MTX concentration monitoring results. In this investigation, 53 were prospective study, 93 were retrospective study. Results showed, totally 75 MTX monitoring literatures were published from Jan. 2005 to Del. 2009 caccounting for 51.4% ; the monitoring method of MTX were mainly FPIA and HPLC; the monitoring time of 43.5% literatures was 24,48,72, 96 h after administration, which was recommenoled by the Food and Drug Administration（FDA） ; 56.1% took use of standard con- centration of MTX （24 h≤ 10 μmol/L, 48 h≤1 μmol/L, 72 h≤0.2 μmol/L）, which was recommended by FDA. In acute lymphoblas- tic leukemia （ALL） and non-Hodgkin lymphoma（NHL）, the beginning time of using CF was generally 36 h after administration, while beginning time of using CF was generally 6 h and 12 h in osteosarcoma; 73.6% stopped to use CF when the MTX concentration under 0.1 μmol/L, while only 8.3% stopped when the MTX concentration under 0.05 μmol/L that was FDA recommended concentration. CONCLUSIONS： The monitoring time points, concentration standard, beginning time of CF and stopping concentration for MTX has not been completely reunificated but researches unanimity. Based on MTX metabolic characteristics of Chinese, it is suggested that relevant departments should establish domestic plasma concentration guidance for MTX to better guide MTX plasma concentration in clinic for individual regimen.