大剂量甲氨蝶呤不同给药持续时间治疗原发性中枢神经系统淋巴瘤的研究

Study on the Treatment of Primary Central Nervous System Lymphoma with Different Infusion Duration of High-Dosage of Methotrexate

目的研究大剂量甲氨蝶呤(HD-MTX)不同给药持续时间治疗原发性中枢神经系统淋巴瘤对患者脑脊液中药物浓度的影响。方法采用自身对照法比较HD-MTX快速滴注(3 h)与常规滴注(6 h)对患者脑脊液中MTX浓度的影响;利用反相高效液相色谱法检测MTX浓度;对不同测量时间点两种给药方式的脑脊液药物浓度进行配对t检验,分析脑脊液药物浓度与血药浓度的相关性。结果HD-MTX快速滴注(3 h)与常规滴注(6 h)给药后第3 h(6.56μmol·L-1 vs.4.40μmol·L-1,P=0.017)、6 h(7.53μmol·L-1 vs.5.03μmol·L-1,P<0.001)、12 h(2.27μmol·L-1 vs.0.63μmol·L-1,P=0.005),患者脑脊液中的药物浓度有显著差异;常规滴注后第12 h,患者脑脊液中的MTX浓度(0.63±0.33)μmol·L-1低于有效治疗浓度,而快速滴注后12 h的浓度(2.27±0.70)μmol·L-1仍维持在有效治疗浓度;患者血药浓度与脑脊液药物浓度无明显相关性(r=0.221)。结论HD-MTX快速滴注(3 h)相比常规滴注(6 h)可显著提高原发性中枢神经系统淋巴瘤患者脑脊液中的MTX浓度,延长药物有效作用时间,且患者耐受良好。

Objective To study the effect of high dosage of methotrexate(HD-MTX)infusion duration on the concentration of drug in the cerebrospinal fluid(CSF)of the patients with primary central nervous system diffuse large B-cell lymphoma.Methods The self-contrast method was employed to compare the influence of HD-MTX rapid infusion(3 h)and regular infusion(6 h)on the concentration of MTX in CSF.The MTX drug concentration was measured by reversed-phase high-performance liquid chromatography.Paired t-test was performed on cerebrospinal fluid drug concentrations in two treatment cycles at different measurement time points,in order to analyze the correlation between the MTX concentration in CSF and that in blood.Results There were significant differences in the MTX concentration in CSF between the ways of rapid infusion(3 h)and regular infusion(6 h)at 3 h(6.56μmol·L-1 vs.4.40μmol·L-1,P=0.017),6 h(7.53μmol·L-1 vs.5.03μmol·L-1,P<0.001),and 12 h(2.27μmol·L-1 vs.0.63μmol·L-1,P=0.005)after the completion of infusion duration of HD-MTX.The concentration of MTX in CSF at 12 h[(2.27±0.70)μmol·L-1]after the rapid infusion still hold the therapeutic effect.However,it was lower than the effective therapeutic concentration at 12 h[(0.63±0.33)μmol·L-1]after regular infusion.The MTX plasma concentration had no significant correlation with the MTX concentration in CSF(r=0.221).Conclusion Compared with the regular infusion(6 h),rapid infusion(3 h)increased the MTX concentration in CSF and prolonged the effective time of MTX,and both regimens were well tolerated.