A Previously Unknown Drug-Drug Interaction Is Suspected in Delayed Elimination of Plasma Methotrexate in High-Dose Methotrexate Therapy
A Previously Unknown Drug-Drug Interaction Is Suspected in Delayed Elimination of Plasma Methotrexate in High-Dose Methotrexate Therapy
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DOI：
10.1177/1060028019870445
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发表时间：
2020-01
影响因子：
2.9
通讯作者：
J. Ishizaki;C. Nakano;Kana Kitagawa;Y. Suga;Y. Sai
中科院分区：
文献类型：
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作者：
J. Ishizaki;C. Nakano;Kana Kitagawa;Y. Suga;Y. Sai
背景：大剂量甲氨蝶呤（HD-MTX）治疗广泛应用于白血病、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浓度的毒性，但仍有许多MTX消除延迟的情况。目的：我们怀疑血清MTX消除延迟是由于MTX与伴随药物之间未知的相互作用引起的。研究方法：关于MTX消除延迟情况下的伴随药物，我们对35例接受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MTX消除延迟的危险因素。结果如下：延迟组中伴随使用复方甘草酸苷（SNMC）（一种甘草酸苷制剂）和长春新碱的百分比较高。接受HD-MTX治疗的患者中MTX消除延迟的百分比为41%。多因素Logistic回归分析显示，单独合并使用SNMC是MTX延迟给药的显著危险因素（比值比= 12.20; 95%CI = 1.06-139.84）。结论和相关性：同时使用SNMC被证明与血清MTX的延迟消除有关，我们的研究结果表明MTX和SNMC之间存在以前未知的药物相互作用。
Background: 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. Objective: We suspected that delayed elimination of serum MTX was caused by unknown interactions between MTX and concomitant drugs. Methods: 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. Results: 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). Conclusion and Relevance: 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.