关键词: 甲氨蝶呤, 骨肉瘤, 药代动力学

Abstract: Objective To evaluate the pharmacokinetics and clinical results in preoperative osteosarcoma patients with HDMTX chemotherapy.Methods The methotrexate pharmacokinetics of 32 osteosarcoma patients who were treated with 37 courses of preoperative HDMTX chemotherapy were analyzed.Chemotherapy protocol: all patients received HDMTX(at the dose of 8～12 g/m²) intravenously with folinic acid rescue(at the dose of 9～15 mg).Patients received hydration and alkalinization fluids starting 24 hr before the MTX administration and continuing 24 hrs after HDMTX administration was completed.Serial blood samples were obtained at 0,1,6,12,24,48 and 72 hours after the MTX infusion.The serum MTX concentrations were measured subsequently.The MTX data were treated with NCA(non-compartment analysis) model.The event free survival time(EFS),change of MR image and the adverse effects of the patients were recorded.Results AUC=4 853.53±1581.53 μmol/(L·h^-1),Cmax=947.79±333.45 μmol/(L·h^-1),EFS=(41.47±16.07)month.EFS has a close correlation with AUC and has none close correlation with the Cmax.Significant differences were detected in EFS considering the AUC of 4 000 μmol/(L·h^-1) as the cut-off point.According to the change of MRI,the cases are divided into two groups: good response group and poor response group,their AUCs and Cmaxs had significant differences.Eleven cases demonstrate marrow inhibition and their AUCs were significantly difference from those without.Four cases demonstrated hepatic impairment.One case complicated oral ulcer.Conclusion AUC has close correlations with the short and long term clinical results.AUC>4000 μmol/(L·h^-1) can be a criterion.Marrow inhibition is related to higher AUC or Cmax.

Key words: methotrexate, osteosarcoma, pharmacokinetics