Objective： To study the cerebrospinal fluid pharmacokinetics of intravenously administered high dose-methotrexate （HD-MTX） and provide a solid fundament for clinical practice. Methods： MTX at a high dose ranging f...Objective： To study the cerebrospinal fluid pharmacokinetics of intravenously administered high dose-methotrexate （HD-MTX） and provide a solid fundament for clinical practice. Methods： MTX at a high dose ranging from 1.0 to 3.0 g per course was intravenously administered to 30 patients with malignant tumors. Blood and CSF samples were consecutively collected up to 36 h after the initiation of infusion （6 h）. MTX concentrations were measured by using a reversed phase high-performance liquid chromatography （RP-HPLC） assay. Results： CSF MTX concentrations were （1.65±1.52）×10^-6, （4.3±3.34）× 10^-7, （1.46±1.10）×10^-7 and （3.19±4.38）×10^-8 mol/L, respectively, at 0, 6, 12 and 24 h post infusion, and became undetectable at 36 h post infusion. The concentration-time curve of CSF MTX closely resembled that of the plasma MTX and fitted with the following linear regression equation： Y=0.057 97＋0.010 82X （Y： CSF MTX concentration, X： Plasma MTX concentration, r=0.8357）. Conclusion： CSF MTX was metabolized in a linear two-compartment model. Additionally, pharmacokinetic analysis of MTX levels indicated a positive correlation between CSF MTX and plasma MTX levels.展开更多
Delayed elimination of methotrexate(MTX) is a major clinical concern in patients receiving high-dose MTX(HD-MTX) therapy. In the present study, we aimed to retrospectively explore the factors associated with MTX conce...Delayed elimination of methotrexate(MTX) is a major clinical concern in patients receiving high-dose MTX(HD-MTX) therapy. In the present study, we aimed to retrospectively explore the factors associated with MTX concentrations and elimination delay in pediatric patients with hematological malignancies. Cycles of HD-MTX therapy were categorized into the normal elimination group and delayed elimination group according to the serum MTX concentrations at 24(C) or 42 h(C) after the start of MTX therapy. Clinical characteristics associated with MTX concentrations and elimination delay were assessed by χ^(2) test, Fisher’s exact test, Mann-Whitney test, or Spearman’s correlation coefficient. Generalized Estimating Equations(GEE) were used to adjust for the clustering effects of multiple cycles in one patient and confounders. A total of 43 patients with 138 cycles of HD-MTX chemotherapy were included and evaluated in the current study. Dose, white blood cells(WBC), hemoglobin(HB), and blood urea nitrogen(BUN) were significantly correlated with MTX C(all P < 0.05). No significant correlations were noticed between baseline characteristics and MTX C. Delayed MTX elimination was observed in 34(24.6%) courses. Dose, WBC, HB, BUN, and concurrent infection were the significant risk factors for delayed MTX elimination(all P < 0.05). Our study identified several risk factors associated with MTX levels and elimination, which might be used to recognize patients with a high risk of delayed MTX elimination. However, the findings need to be confirmed in further large-scale studies.展开更多
文摘Objective： To study the cerebrospinal fluid pharmacokinetics of intravenously administered high dose-methotrexate （HD-MTX） and provide a solid fundament for clinical practice. Methods： MTX at a high dose ranging from 1.0 to 3.0 g per course was intravenously administered to 30 patients with malignant tumors. Blood and CSF samples were consecutively collected up to 36 h after the initiation of infusion （6 h）. MTX concentrations were measured by using a reversed phase high-performance liquid chromatography （RP-HPLC） assay. Results： CSF MTX concentrations were （1.65±1.52）×10^-6, （4.3±3.34）× 10^-7, （1.46±1.10）×10^-7 and （3.19±4.38）×10^-8 mol/L, respectively, at 0, 6, 12 and 24 h post infusion, and became undetectable at 36 h post infusion. The concentration-time curve of CSF MTX closely resembled that of the plasma MTX and fitted with the following linear regression equation： Y=0.057 97＋0.010 82X （Y： CSF MTX concentration, X： Plasma MTX concentration, r=0.8357）. Conclusion： CSF MTX was metabolized in a linear two-compartment model. Additionally, pharmacokinetic analysis of MTX levels indicated a positive correlation between CSF MTX and plasma MTX levels.
基金National Natural Science Foundation of China (Grant No. 81872926 and No. 81503135)Beijing Municipal Administration of Hospitals’ Youth Programme (Grant No. QML20160703)+1 种基金Enhancement Fun ding of Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use (BZ0439)Science and Technology Fund of Beijing Shijitan Hospital (Grant No. 2017-c01)。
文摘Delayed elimination of methotrexate(MTX) is a major clinical concern in patients receiving high-dose MTX(HD-MTX) therapy. In the present study, we aimed to retrospectively explore the factors associated with MTX concentrations and elimination delay in pediatric patients with hematological malignancies. Cycles of HD-MTX therapy were categorized into the normal elimination group and delayed elimination group according to the serum MTX concentrations at 24(C) or 42 h(C) after the start of MTX therapy. Clinical characteristics associated with MTX concentrations and elimination delay were assessed by χ^(2) test, Fisher’s exact test, Mann-Whitney test, or Spearman’s correlation coefficient. Generalized Estimating Equations(GEE) were used to adjust for the clustering effects of multiple cycles in one patient and confounders. A total of 43 patients with 138 cycles of HD-MTX chemotherapy were included and evaluated in the current study. Dose, white blood cells(WBC), hemoglobin(HB), and blood urea nitrogen(BUN) were significantly correlated with MTX C(all P < 0.05). No significant correlations were noticed between baseline characteristics and MTX C. Delayed MTX elimination was observed in 34(24.6%) courses. Dose, WBC, HB, BUN, and concurrent infection were the significant risk factors for delayed MTX elimination(all P < 0.05). Our study identified several risk factors associated with MTX levels and elimination, which might be used to recognize patients with a high risk of delayed MTX elimination. However, the findings need to be confirmed in further large-scale studies.
