【摘要】 目的验证大剂量甲氨蝶呤(MTX)化学治疗(化疗)中给药开始48 h点血药浓度(C48 h)对于预判消除相末端药动学特征和毒副反应的可靠性,为临床制订合理的解救治疗方案提供依据。方法急性淋巴细胞白血病患儿114例,行HDMTX化疗176次,MTX剂量为3~5 g·(m2)-1,24 h持续静脉滴注。用固相萃取高效液相色谱法测定MTX用药后24,48,72 h血清中MTX浓度。病例按C48 h≥1μmol·L-1和C48 h<1μmol·L-1分组,采用残数法计算两组的消除相药动学参数,采用Ridit分析比较两组的毒副反应差异。结果 C48 h≥1μmol·L-1组的C72 h和AUC48-∞均显著高于C48 h<1μmol·L-1组(P<0.01);C48 h≥1μmol·L-1组在血液系统、胃肠系统和肝胆系统的毒副反应也显著强于C48 h<1μmol·L-1组(P<0.05)。C48 h≥1μmol·L-1组解救天数(5.02±1.65)d,C48 h<1μmol·L-1组解救天数为(3.05±0.21)d。结论 C48 h可以很好地预测MTX消除相末端的药动学特征和毒副反应,C48 h≥1μmol·L-1可以作为MTX消除延迟的临床诊断依据以指导后期解救。更多还原

【Abstract】 Objective To recheck the reliability of methotrexate( MTX) serum concentration at 48 h( C48 h) in predicting the pharmacokinetic characteristics and toxic reactions at terminal elimination phase after high dose MTX infusion and to provide a reference for determination of rational rescue regimen in clinic practice. Methods In total,114 cases of children with acute lymphoblastic leukemia( ALL) received 176 courses of high dose MTX chemotherapy treatment. The regimen was continuous infusion of MTX[3-5 g·( m2)-1]in 24 h. Plasma samples were treated with solid phase extraction and serum concentrations of MTX were determined by HPLC at 24,48 and 72 h(C24 h,C48 hand C72 h) after starting MTX infusion. All data were divided into C48 h≥1 μmol·L-1group and C48 h< 1 μmol·L-1group. The pharmacokinetic parameters of the two groups at elimination phase were estimated by residual method and the toxic reactions after MTX infusion of two groups were compared by Ridit analysis. Results The C72 hand AUC48-∞were significantly higher in C48 h≥1 μmol·L-1group than in C48 h<1 μmol·L-1group(P < 0. 01). The MTX toxicities to the blood,digestive and hepatic systems were significantly higher in C48 h≥1 μmol·L-1group than in C48 h< 1 μmol·L-1group( P < 0. 05). Conclusion C48 hcan predict the pharmacokinetic characteristics and toxic reactions at ther terminal elimination phase. Therefore,C48 h≥1 μmol·L-1can be used as a marker of MTX elimination delay event to guide later rescue regimen.更多还原