DAILY PROFILES OF PLASMA PHENYLALANINE AND TYROSINE IN PATIENTS WITH OSTEOGENIC-SARCOMA DURING TREATMENT WITH HIGH-DOSE METHOTREXATE-CITROVORUM RESCUE
DAILY PROFILES OF PLASMA PHENYLALANINE AND TYROSINE IN PATIENTS WITH OSTEOGENIC-SARCOMA DURING TREATMENT WITH HIGH-DOSE METHOTREXATE-CITROVORUM RESCUE
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DOI：
10.1002/mpo.2950170404
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发表时间：
1989-01-01
期刊：
影响因子：
--
通讯作者：
PATEL, CC
中科院分区：
文献类型：
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作者：
HILTON, MA;BERTOLONE, S;PATEL, CC
三名青少年和一名儿童骨肉瘤进行了研究，在多个疗程的高剂量甲氨蝶呤，柠檬酸因子救援（HDMTX-CFR），与一名青少年间歇治疗超过6年。血浆苯丙氨酸（Phe）和酪氨酸（Tyr）在MTX输注前立即测定，然后每天测定，直至血清MTX降至10 - 7 M以下。在24小时时，均显示Phe和Phe/Tyr比率显著增加。这表明抑制二氢蝶啶还原酶（DHPR），其与肝Phe羟化酶相关，控制Phe的血浆浓度。这种酶系统的抑制不被CFR缓解。在青少年患者中，尽管血浆中MTX水平稳步下降，但Phe浓度在24至48小时内下降，在4 - 7天升至新的峰值。这种二次增加的可能原因进行了讨论。暴露于HDMTx时间最长的患者显示治疗前Phe/Tyr比率随时间增加，表明肝功能标准试验未显示肝实质细胞损伤。在HDMTX-CFR过程中评价血浆Phe可允许评估肝中MTX或其代谢物的细胞内浓度，而不受CFR干扰。
Three adolescents and one child with osteosarcoma were studied during multiple courses of high-dose methotrexate, citrovorum factor rescue (HDMTX-CFR), with one adolescent treated intermittently over a period of 6 years. Plasma phenylalanine (Phe) and Tyrosine (Tyr) were measured immediately before the infusion of MTX and then daily until serum MTX fell below 10-7 M. At 24 hours, all showed marked increases in Phe and in the Phe/Tyr ratio. This suggests inhibition of dihydropteridine reductase (DHPR) which, in association with hepatic Phe hydroxylase, controls plasma concentrations of Phe. Inhibition of this enzyme system is not relieved by CFR. In the adolescent patients, although MTX levels in plasma declined steadily, Phe concentrations, which fell between 24 and 48 hours, rose to a new peak at 4-7 days. Possible reasons for this secondary increases are discussed. The patient with the longest exposure to HDMTx showed an increase in pretreatment Phe/Tyr ratios with time, suggesting damage to liver parenchymal cells not indicated by standard tests of liver function. Evaluation of plasma Phe during the course of HDMTX-CFR may permit assessment of intracellular concentrations of MTX or its metabolites in the liver without interference by CFR.