• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

肾功能和血浆甲氨蝶呤浓度可预测接受大剂量甲氨蝶呤治疗的成年人的毒性。

Renal Function and Plasma Methotrexate Concentrations Predict Toxicities in Adults Receiving High-Dose Methotrexate.

机构信息

Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).

出版信息

Med Sci Monit. 2018 Oct 29;24:7719-7726. doi: 10.12659/MSM.912999.

DOI:10.12659/MSM.912999
PMID:30369593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6216510/
Abstract

BACKGROUND Methotrexate (MTX) is an effective drug for the treatment of adult malignancies, but toxicity remains a significant problem. Toxic reactions may occur when patients use high-dose MTX (HD-MTX), but the correlation between its toxicity and concentration in adults is controversial. The purpose of this study was to examine the relationship between MTX concentration and renal function, as well as to assess toxic reactions to MTX in Chinese adults with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). MATERIAL AND METHODS This retrospective study enrolled 97 patients who had been diagnosed with ALL or NHL, and who were treated at the Hemopathology Department of Shanghai Changhai Hospital from January 2015 to June 2016. RESULTS Forty-one (27.5%) episodes of elimination delay were observed. We found negative correlations between creatinine clearance rate before MTX infusion and the plasma concentrations of MTX at 36 h after MTX infusion (P=0.005). The serum creatinine at 48 h and plasma concentrations of MTX at 48 h and72 h were significantly and positively correlated (both p=0.000). High blood concentration of MTX was positively associated with nephrotoxicity > grade 1 (P<0.01). Infection > grade 1 was more likely to occur if a patient had high MTX levels at 36 h,48 h, and 72 h (P<0.01). CONCLUSIONS Our results show that renal function is associated with MTX concentration, and high MTX concentration can predict the occurrence of renal toxicity and infection related to MTX.

摘要

背景

甲氨蝶呤(MTX)是治疗成人恶性肿瘤的有效药物,但毒性仍然是一个重大问题。当患者使用高剂量 MTX(HD-MTX)时可能会发生毒性反应,但 MTX 毒性与其在成人中的浓度之间的相关性存在争议。本研究旨在探讨 MTX 浓度与肾功能之间的关系,并评估其在中国成人急性淋巴细胞白血病(ALL)和非霍奇金淋巴瘤(NHL)中的毒性反应。

材料和方法

这项回顾性研究纳入了 2015 年 1 月至 2016 年 6 月在上海长海医院血液病理科诊断为 ALL 或 NHL 的 97 例患者。

结果

观察到 41 例(27.5%)消除延迟。我们发现 MTX 输注前肌酐清除率与 MTX 输注后 36 小时血浆浓度呈负相关(P=0.005)。48 小时血清肌酐和 48 小时及 72 小时血浆 MTX 浓度呈显著正相关(均 p=0.000)。MTX 血药浓度高与>1 级肾毒性呈正相关(P<0.01)。如果患者在 36 小时、48 小时和 72 小时 MTX 水平较高,则更有可能发生>1 级感染(P<0.01)。

结论

我们的结果表明,肾功能与 MTX 浓度相关,高 MTX 浓度可预测 MTX 相关肾毒性和感染的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cc/6216510/510740a7ad24/medscimonit-24-7719-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cc/6216510/b22e5c7d665e/medscimonit-24-7719-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cc/6216510/510740a7ad24/medscimonit-24-7719-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cc/6216510/b22e5c7d665e/medscimonit-24-7719-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cc/6216510/510740a7ad24/medscimonit-24-7719-g002.jpg

相似文献

1
Renal Function and Plasma Methotrexate Concentrations Predict Toxicities in Adults Receiving High-Dose Methotrexate.肾功能和血浆甲氨蝶呤浓度可预测接受大剂量甲氨蝶呤治疗的成年人的毒性。
Med Sci Monit. 2018 Oct 29;24:7719-7726. doi: 10.12659/MSM.912999.
2
Effect of polymorphisms within methotrexate pathway genes on methotrexate toxicity and plasma levels in adults with hematological malignancies.甲氨蝶呤代谢途径基因多态性对血液系统恶性肿瘤成人患者甲氨蝶呤毒性和血药浓度的影响。
Pharmacogenomics. 2014 Aug;15(11):1479-94. doi: 10.2217/pgs.14.97.
3
Serum creatinine and creatinine clearance for predicting plasma methotrexate concentrations after high-dose methotrexate chemotherapy for the treatment for childhood lymphoblastic malignancies.血清肌酐和肌酐清除率预测儿童急性淋巴细胞白血病大剂量甲氨蝶呤化疗后血药浓度。
Cancer Chemother Pharmacol. 2014 Jan;73(1):79-86. doi: 10.1007/s00280-013-2319-2. Epub 2013 Oct 25.
4
Creatinine clearance rate and serum creatinine concentration are related to delayed methotrexate elimination in children with lymphoblastic malignancies.肌酐清除率和血清肌酐浓度与儿童急性淋巴细胞白血病中甲氨蝶呤消除延迟有关。
Neoplasma. 2014;61(1):77-82.
5
High-dose methotrexate: on the relationship of methotrexate elimination time vs renal function and serum methotrexate levels in 1164 courses in 264 Swedish children with acute lymphoblastic leukaemia (ALL).大剂量甲氨蝶呤:关于264名瑞典急性淋巴细胞白血病(ALL)儿童的1164个疗程中甲氨蝶呤清除时间与肾功能及血清甲氨蝶呤水平的关系
Cancer Chemother Pharmacol. 2003 Apr;51(4):311-20. doi: 10.1007/s00280-002-0552-1. Epub 2003 Mar 28.
6
Methotrexate Associated Renal Impairment Is Related to Delayed Elimination of High-Dose Methotrexate.甲氨蝶呤相关的肾损害与高剂量甲氨蝶呤清除延迟有关。
ScientificWorldJournal. 2015;2015:751703. doi: 10.1155/2015/751703. Epub 2015 Jun 21.
7
Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.血清肌酐与血浆甲氨蝶呤水平用于预测接受高剂量甲氨蝶呤治疗儿童的毒性反应
Pediatr Hematol Oncol. 2015;32(8):576-84. doi: 10.3109/08880018.2015.1087612. Epub 2015 Nov 11.
8
Statistical analysis of relation between plasma methotrexate concentration and toxicity in high-dose methotrexate therapy of childhood nonHodgkin lymphoma.儿童非霍奇金淋巴瘤大剂量甲氨蝶呤治疗中血浆甲氨蝶呤浓度与毒性关系的统计分析
Pediatr Blood Cancer. 2015 Feb;62(2):279-284. doi: 10.1002/pbc.25305. Epub 2014 Oct 30.
9
Comparison of pharmacokinetics and toxicity after high-dose methotrexate treatments in children with acute lymphoblastic leukemia.儿童急性淋巴细胞白血病大剂量甲氨蝶呤治疗后的药代动力学和毒性比较。
Anticancer Drugs. 2013 Feb;24(2):189-97. doi: 10.1097/CAD.0b013e32835b8662.
10
Assessment of renal function during high-dose methotrexate treatment in children with acute lymphoblastic leukemia.急性淋巴细胞白血病患儿大剂量甲氨蝶呤治疗期间的肾功能评估
Pediatr Blood Cancer. 2014 Dec;61(12):2199-202. doi: 10.1002/pbc.25137. Epub 2014 Aug 31.

引用本文的文献

1
Combating Methotrexate Resistance in Cancer Treatment: A Review on Navigating Pathways and Enhancing Its Efficacy With Fat-Soluble Vitamins.癌症治疗中对抗甲氨蝶呤耐药性:关于通过脂溶性维生素探寻途径并提高其疗效的综述
Scientifica (Cairo). 2025 Apr 16;2025:8259470. doi: 10.1155/sci5/8259470. eCollection 2025.
2
A European consensus recommendation on the management of delayed methotrexate elimination: supportive measures, leucovorin rescue and glucarpidase treatment.欧洲关于甲氨蝶呤消除延迟管理的共识性建议:支持措施、亚叶酸钙解救及羧肽酶G2治疗。
J Cancer Res Clin Oncol. 2024 Oct 2;150(10):441. doi: 10.1007/s00432-024-05945-6.
3

本文引用的文献

1
Preventing and Managing Toxicities of High-Dose Methotrexate.预防和管理大剂量甲氨蝶呤的毒性反应
Oncologist. 2016 Dec;21(12):1471-1482. doi: 10.1634/theoncologist.2015-0164. Epub 2016 Aug 5.
2
Pharmacogenetics of methotrexate in acute lymphoblastic leukaemia: why still at the bench level?甲氨蝶呤在急性淋巴细胞白血病中的药物遗传学:为何仍停留在实验阶段?
Eur J Clin Pharmacol. 2014 Mar;70(3):253-60. doi: 10.1007/s00228-013-1623-4. Epub 2013 Dec 27.
3
High incidence of methotrexate associated renal toxicity in patients with lymphoma: a retrospective analysis.
Early clinical indicators of acute kidney injury caused by administering high-dose methotrexate therapy to juvenile pigs.
对幼年猪施用高剂量甲氨蝶呤疗法所致急性肾损伤的早期临床指标。
Front Nephrol. 2023 Sep 12;3:1193494. doi: 10.3389/fneph.2023.1193494. eCollection 2023.
4
A Rapid Method for Determination of Serum Methotrexate Using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application in Therapeutic Drug Monitoring.一种使用超高效液相色谱-串联质谱法测定血清甲氨蝶呤的快速方法及其在治疗药物监测中的应用。
J Lab Physicians. 2023 Jan 18;15(3):344-353. doi: 10.1055/s-0042-1760668. eCollection 2023 Sep.
5
Effects of genetic polymorphisms on methotrexate levels and toxicity in Chinese patients with acute lymphoblastic leukemia.基因多态性对中国急性淋巴细胞白血病患者甲氨蝶呤血药浓度及毒性的影响
Blood Sci. 2022 Nov 11;5(1):32-38. doi: 10.1097/BS9.0000000000000142. eCollection 2023 Jan.
6
The Nephrotoxicity of Drugs Used in Causal Oncological Therapies.用于因果性肿瘤治疗的药物的肾毒性。
Curr Oncol. 2022 Dec 8;29(12):9681-9694. doi: 10.3390/curroncol29120760.
7
Successful Treatment of Acute Uric Acid Nephropathy with Rasburicase in a Primary Central Nervous System Lymphoma Patient Showing a Dramatic Response to Methotrexate-Case Report.在一名对甲氨蝶呤有显著反应的原发性中枢神经系统淋巴瘤患者中,用拉布立酶成功治疗急性尿酸肾病——病例报告
J Clin Med. 2022 Sep 22;11(19):5548. doi: 10.3390/jcm11195548.
8
Extracorporeal Treatment for Methotrexate Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.体外治疗甲氨蝶呤中毒:EXTRIP 工作组的系统评价和建议。
Clin J Am Soc Nephrol. 2022 Apr;17(4):602-622. doi: 10.2215/CJN.08030621. Epub 2022 Mar 2.
9
Relationship Between the Free and Total Methotrexate Plasma Concentration in Children and Application to Predict the Toxicity of HD-MTX.儿童血浆中游离甲氨蝶呤与总甲氨蝶呤浓度的关系及其在预测大剂量甲氨蝶呤毒性中的应用
Front Pharmacol. 2021 Apr 29;12:636975. doi: 10.3389/fphar.2021.636975. eCollection 2021.
10
Diabetes is a risk factor for high-dose methotrexate-associated AKI in lymphoma patients.糖尿病是淋巴瘤患者中高剂量甲氨蝶呤相关急性肾损伤的一个风险因素。
Ren Fail. 2020 Nov;42(1):1111-1117. doi: 10.1080/0886022X.2020.1838926.
淋巴瘤患者中与甲氨蝶呤相关的肾毒性发生率高:一项回顾性分析
Leuk Lymphoma. 2014 Jun;55(6):1345-9. doi: 10.3109/10428194.2013.840780. Epub 2013 Nov 1.
4
Nephrotoxicity from chemotherapeutic agents: clinical manifestations, pathobiology, and prevention/therapy.化疗药物所致肾毒性:临床表现、病理生物学及预防/治疗。
Semin Nephrol. 2010 Nov;30(6):570-81. doi: 10.1016/j.semnephrol.2010.09.005.
5
Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome.甲氨蝶呤致肾功能障碍时用葡醛内酯、亚叶酸钙和胸苷解救:影响疗效的临床和药理学因素。
J Clin Oncol. 2010 Sep 1;28(25):3979-86. doi: 10.1200/JCO.2009.25.4540. Epub 2010 Aug 2.
6
Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma.静脉注射甲氨蝶呤作为中枢神经系统 (CNS) 预防措施,与高危弥漫性大 B 细胞淋巴瘤患者的 CNS 复发风险低相关。
Cancer. 2010 Sep 15;116(18):4283-90. doi: 10.1002/cncr.25278.
7
Advances in individual prediction of methotrexate toxicity: a review.甲氨蝶呤毒性个体预测的进展:综述
Br J Haematol. 2009 Sep;146(5):489-503. doi: 10.1111/j.1365-2141.2009.07765.x. Epub 2009 Jun 15.
8
Ancestry and pharmacogenetics of antileukemic drug toxicity.抗白血病药物毒性的血统与药物遗传学
Blood. 2007 May 15;109(10):4151-7. doi: 10.1182/blood-2006-10-054528. Epub 2007 Jan 30.
9
High-dose methotrexate and/or leucovorin rescue for the treatment of children with lymphoblastic malignancies: do we really know why, when and how?大剂量甲氨蝶呤和/或亚叶酸钙解救用于治疗儿童淋巴细胞性恶性肿瘤:我们真的知道原因、时机和方法吗?
Neoplasma. 2005;52(6):456-63.
10
High-dose methotrexate in acute lymphoblastic leukemia: where is the evidence for its continued use?大剂量甲氨蝶呤治疗急性淋巴细胞白血病:其持续应用的证据何在?
Pharmacotherapy. 2005 May;25(5):748-55. doi: 10.1592/phco.25.5.748.63584.