Ronchera C L, Hernández T, Peris J E, Torres F, Granero L, Jiménez N V, Plá J M
Department of Pharmacy, Hospital Dr Peset, Valencia, Spain.
Ther Drug Monit. 1993 Oct;15(5):375-9. doi: 10.1097/00007691-199310000-00004.
A case report of toxicity following concurrent administration of high-dose methotrexate and amoxycillin is presented. A 16-year-old male patient was administered 10 high-dose methotrexate cycles for treatment of a fully malignant osteogenic sarcoma. Methotrexate was administered at a dosage of 8 g/m2 and infused intravenously over a 6-h period. The patient received pre- and posttreatment hydration and sodium bicarbonate for alkalinization of urine. Calcium folinate rescue was performed when appropriate. During the 10th cycle, coadministration of amoxycillin (1 g/6 h, p.o.) resulted in prolonged and marked enhancement of methotrexate serum levels. Pharmacokinetic parameters obtained in cycle 10 indicate significant differences for total plasma clearance, mean residence time, and distribution half-life when compared to those in cycles 1-9. Amoxycillin decreased the renal clearance of methotrexate, probably by competition at the common tubular secretion system and by secondary methotrexate-induced renal impairment. The patient experienced acute and subacute toxicity with renal failure, myelosuppression, mucositis, nausea, vomiting, fever, and dermatologic abnormalities. Patients receiving amoxycillin during methotrexate therapy should be closely monitored to avoid severe toxicity.
本文报告了一例高剂量甲氨蝶呤与阿莫西林同时给药后出现毒性反应的病例。一名16岁男性患者接受了10个周期的高剂量甲氨蝶呤治疗，以治疗完全恶性的骨肉瘤。甲氨蝶呤的给药剂量为8 g/m²，静脉滴注6小时。患者在治疗前和治疗后接受了补液和碳酸氢钠以碱化尿液。在适当的时候进行了亚叶酸钙解救。在第10个周期中，同时给予阿莫西林（1 g/6小时，口服）导致甲氨蝶呤血清水平延长且显著升高。与第1 - 9个周期相比，第10个周期获得的药代动力学参数表明总血浆清除率、平均驻留时间和分布半衰期存在显著差异。阿莫西林可能通过在共同的肾小管分泌系统竞争以及继发于甲氨蝶呤的肾损伤而降低了甲氨蝶呤的肾清除率。该患者经历了急性和亚急性毒性反应，包括肾衰竭、骨髓抑制、粘膜炎、恶心、呕吐、发热和皮肤异常。在甲氨蝶呤治疗期间接受阿莫西林的患者应密切监测，以避免严重毒性反应。
