急性淋巴细胞白血病用甲氨喋啶治疗的动力学研究

Study on chemotherapeutic individualization of hing does methotrexate in acute lymphoblastic leukemia

目的 :根据不同年龄 ,采用两种不同大剂量甲氨喋啶 2 4h持续静滴下的稳态血药浓度及毒性反应。方法 :分别于甲氨喋啶静滴开始后 1、6、2 3、44、6 8h点采集静脉血 2 ml及 1、2 4h点脑脊液 2 m l,应用免疫偏振荧光法检测血清与脑脊液 MTX浓度。结果 :9例老年组采用 2 g· M- 2 剂量 ,在 1、6、2 3、44、6 8h点血清 MTX浓度分别为 5 6 .97± 4.7μmol/ L、40 .46± 7.0 6μmol/ L、17.31± 9.76μm ol/ L、0 .91± 1.34μm ol/ L、0 .2 5± 0 .2 2μmol/L ;在 1、2 4h点脑脊液 MTX浓度分别为 0 .38± 0 .2 4μm ol/ L、2 .0 7± 0 .76μmol/ L。 16例中青年组采用 3 g· M- 2剂量 ,各小时点血清 MTX浓度分别为 82 .15± 12 .13μmol/ L、6 2 .33± 10 .0 6μm ol/ L、14.75± 7.0 6μm ol/ L、1.71± 1.6 8μm ol/ L、0 .45± 0 .44 μmol/ L;脑脊液 MTX浓度分别为 0 .5 4± 0 .35 μmol/ L、1.96± 0 .5 2 μm ol/ L。结论 :此两种剂量能达到急性淋巴细胞白血病 (AL L)细胞聚谷氨酸盐 MTX饱和所需的剂量 ,毒性反应是可以接受的。

Objective:To observe the state plasma concentration (CSS) and side effects with two different dosages of high dose methotrexate (MTX) by continuous intravenous injection for 24 hours on the basis of different ages.Method:2 milliliter blood samples were collected at 1?6?23?44?68 hours and 2 milliliter cerebrospinal fluid (CSF) beginning the MTX infusion.The levels of MTX were measured by the fluorescence polarization immunoassay (FPIA).Result:The blood levels of MTX in 9 elder patients given 2 g·M -2 each time at 1?6?23?44?68 hour beginning the MTX infusion were 56.97 ± 14.7 μmol/L? 40.46 ± 7.06 μmol/L? 17.31 ± 9.76 μmol/L? 0.91 ± 1.34 μmol/L? 0.25 ± 0.22 μmol/L,The CSF levels of MTX each time at 1?24 hours were 0.38 ± 0.24 μmol/L? 2.07 ± 10.06 μmol/L.The blood levels of MTX in 16 adult patients given 3 g·M -2 each time were 82.15 ± 12.13 μmol/L? 62.33 ± 10.06 μmol/L? 14.75 ± 7.06 μmol/L? 1.71 ± 1.68 μmol/L? 0.45 ± 0.44 μmol/L,The CSF levels of MTX each time were 0.54 ± 0.35 μmol/L? 1.96 ± 0.52 μmol/L.Conclusion:The CSS of MTX could achieve optimal intracellular accumulation of MTX polyglutamates (MTXPG) with two different dosages in acute lymphoblastic leukemia,and the side effects are acceptable.