a Clinical Toxicology Unit , Princess Alexandra Hospital , Brisbane , Australia.
b School of Medicine , University of Queensland , Brisbane , Australia.
Clin Toxicol (Phila). 2018 Dec;56(12):1204-1206. doi: 10.1080/15563650.2018.1484128. Epub 2018 Jul 5.
Acute methotrexate overdose rarely causes systemic toxicity due to saturable absorption and rapid renal elimination. We present a case of methotrexate toxicity following acute overdose.
A 56-year-old female presented soon after an overdose of 1250 mg of methotrexate, zopiclone and tramadol. The methotrexate was initially under-reported (500 mg) and folinic acid was not provided. Despite normal renal function, the patient developed toxicity. She represented 5 days following the overdose with mucositis, bone marrow suppression and prolonged febrile neutropenia. Treatment included folinic acid, broad-spectrum antibiotics, filgrastim, red cell and platelet transfusion. Her bone marrow began to recover 12 days following the overdose. She was discharged home on Day 17.
Severe toxicity following an acute ingestion of a large amount of methotrexate is rarely reported. The development of toxicity was unexpected in this case given methotrexate's pharmacokinetics and the patient's normal renal function. The serum methotrexate concentrations were below the treatment threshold of the folinic acid rescue therapy nomogram suggesting that the nomogram should not be relied on in acute ingestions. Large acute oral methotrexate poisoning can result in systemic toxicity and folinic acid therapy should be provided in ingestions >1000 mg.
急性甲氨蝶呤过量很少引起全身毒性，因为其吸收具有饱和性，且可快速经肾脏排泄。我们报告了一例急性过量服用甲氨蝶呤引起的毒性病例。
一名 56 岁女性在服用 1250mg 甲氨蝶呤、佐匹克隆和曲马多后不久过量服用。甲氨蝶呤最初报告的剂量（500mg）不准确，且未给予亚叶酸钙。尽管肾功能正常，该患者仍出现毒性反应。她在过量服用后 5 天出现黏膜炎、骨髓抑制和发热性中性粒细胞减少症。治疗包括亚叶酸钙、广谱抗生素、非格司亭、红细胞和血小板输注。她的骨髓在过量服用后 12 天开始恢复。第 17 天出院回家。
大量急性摄入甲氨蝶呤后出现严重毒性的情况很少见。鉴于甲氨蝶呤的药代动力学和患者的正常肾功能，该病例发生毒性反应是出乎意料的。血清甲氨蝶呤浓度低于亚叶酸钙解救治疗图谱的治疗阈值，表明图谱不能用于急性摄入。大剂量急性口服甲氨蝶呤中毒可导致全身毒性，摄入超过 1000mg 时应给予亚叶酸钙治疗。
