Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).
Med Sci Monit. 2018 Oct 29;24:7719-7726. doi: 10.12659/MSM.912999.
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.
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。
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。
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)。
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。