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[大剂量甲氨蝶呤后给予羧肽酶-G2。治疗与药物相互作用]

[Carboxypeptidase-G2 administration after high-dose methotrexate. Treatment and drug interactions].

作者信息

Cózar Olmo J A, Martínez Colmenero C, Peláez Pleguezuelos I, Leiva Gea I, López García A B, de la Cruz Moreno J

机构信息

Unidad Gestión Clínica de Pediatría, Unidad Oncohematología, Complejo Hospitalario de Jaén, Jaén, España.

出版信息

An Pediatr (Barc). 2009 Sep;71(3):230-4. doi: 10.1016/j.anpedi.2009.05.014. Epub 2009 Jul 18.

DOI:10.1016/j.anpedi.2009.05.014
PMID:19617010
Abstract

Methotrexate (MTX) is widely used as anticancer agent in various malignancies, including acute lymphoblastic leukaemia, lymphoma and osteosarcoma. High doses of MTX may cause acute renal dysfunction. Nephrotoxicity is prevented by the use of alkalinization and hydration. More recently Carboxypeptidase-G2, a recombinant bacterial enzyme that rapidly hydrolyzes MTX to inactive metabolites, has become available for the treatment of acute nephrotoxicity. On the other hand, glutamine is usually administered in oncology treatments to avoid other side effects. We report a case of an adolescent who was diagnosed with T lymphoblastic lymphoma. He was receiving treatment with glutamine when the third course of methotrexate was administered (5 g/m(2)) and he suffered a deterioration in his renal function. Carboxypeptidase was used but the methotrexate serum concentration reduction was not satisfactory. The technique to assess the amount of enzyme-inactivated methotrexate by quantification of MTX metabolites is not available in our country, therefore, the concentrations of MTX may be overestimated. The literature was reviewed to study the influence of glutamine on delayed methotrexate elimination which may lead to acute toxicity.

摘要

甲氨蝶呤(MTX)作为抗癌药物被广泛应用于各种恶性肿瘤,包括急性淋巴细胞白血病、淋巴瘤和骨肉瘤。高剂量的MTX可能会导致急性肾功能障碍。通过碱化和水化可预防肾毒性。最近,羧肽酶G2,一种能迅速将MTX水解为无活性代谢产物的重组细菌酶,已可用于治疗急性肾毒性。另一方面,在肿瘤治疗中通常会使用谷氨酰胺以避免其他副作用。我们报告一例被诊断为T淋巴母细胞淋巴瘤的青少年病例。在给予第三疗程甲氨蝶呤(5 g/m²)时,他正在接受谷氨酰胺治疗,随后出现肾功能恶化。使用了羧肽酶,但甲氨蝶呤血清浓度降低并不理想。我国尚无通过定量MTX代谢产物来评估酶灭活甲氨蝶呤量的技术,因此,MTX的浓度可能被高估。我们查阅了文献以研究谷氨酰胺对甲氨蝶呤延迟消除的影响,这可能导致急性毒性。

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[Carboxypeptidase-G2 administration after high-dose methotrexate. Treatment and drug interactions].[大剂量甲氨蝶呤后给予羧肽酶-G2。治疗与药物相互作用]
An Pediatr (Barc). 2009 Sep;71(3):230-4. doi: 10.1016/j.anpedi.2009.05.014. Epub 2009 Jul 18.
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Understanding and managing methotrexate nephrotoxicity.了解和管理甲氨蝶呤肾毒性。
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Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2.鞘内注射羧肽酶G2治疗鞘内甲氨蝶呤意外过量
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Delayed elimination of high-dose methotrexate and use of carboxypeptidase G2 in pediatric patients during treatment for acute lymphoblastic leukemia.大剂量甲氨蝶呤在儿童急性淋巴细胞白血病治疗中的延迟清除及羧肽酶G2的应用
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Carboxypeptidase-G2 rescue in a patient with high dose methotrexate-induced nephrotoxicity.羧肽酶G2对一名高剂量甲氨蝶呤诱导的肾毒性患者的救治作用
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