Kanazawa University, Kanazawa, Japan.
Ann Pharmacother. 2020 Jan;54(1):29-35. doi: 10.1177/1060028019870445. Epub 2019 Aug 15.
High-dose methotrexate (HD-MTX) therapy is widely implemented for leukemia, osteosarcoma, and lymphoma. Although various measures have been taken to avoid toxicity from high serum MTX concentrations, there are many cases of delayed elimination of MTX. We suspected that delayed elimination of serum MTX was caused by unknown interactions between MTX and concomitant drugs. Concerning concomitant drugs in the case of delayed elimination of MTX, we performed screening tests in 35 patients who had undergone HD-MTX therapy. We then investigated the risk factors for delayed MTX elimination in 94 patients with leukemia, lymphoma, or osteosarcoma retrospectively. The percentages of concomitant use of Stronger Neo-Minophagen C (SNMC), a glycyrrhizin preparation, and vincristine were higher in the delayed group. The percentage of delayed MTX elimination in patients receiving HD-MTX therapy was 41%. Multiple logistic regression analysis revealed that the concomitant use of SNMC solely was a significant risk factor for delayed MTX (odds ratio = 12.20; 95% CI = 1.06-139.84). Concomitant use of SNMC was shown to be related to delayed elimination of serum MTX, and our results suggested a previously unknown drug-drug interaction between MTX and SNMC.
大剂量甲氨蝶呤（HD-MTX）疗法广泛应用于白血病、骨肉瘤和淋巴瘤。尽管已经采取了各种措施来避免高血清 MTX 浓度引起的毒性，但仍有许多 MTX 消除延迟的病例。我们怀疑 MTX 与伴随药物之间未知的相互作用导致血清 MTX 消除延迟。对于 MTX 消除延迟的伴随药物，我们对 35 名接受 HD-MTX 治疗的患者进行了筛选试验。然后，我们回顾性研究了 94 例白血病、淋巴瘤或骨肉瘤患者延迟 MTX 消除的危险因素。在延迟组中，使用更昔洛韦、甘草酸制剂 SNMC 和长春新碱的比例较高。接受 HD-MTX 治疗的患者中 MTX 消除延迟的比例为 41%。多变量逻辑回归分析显示，仅使用 SNMC 是 MTX 延迟的显著危险因素（比值比=12.20；95%可信区间=1.06-139.84）。SNMC 的联合使用与血清 MTX 消除延迟有关，我们的结果提示 MTX 和 SNMC 之间存在以前未知的药物相互作用。
