| Objective: Acute lymphoblastic Leukemia (ALL) is a kind of malignant tumour of the hemopoietic system. High-dose methotrexate (HD-MTX) in the solution for chemotherapy of ALL is the primary chemotherapeutic drug to prevent central nervous system leukemia(CNSL). This study aims to discuss the pharmacodynamics and toxicology of HD-MTX, 3.0g/m2 and 5.0g/m2 (in terms of body surface area), at the points of 24h, 44h, 68h after adiminstration, so as to improve the therapeutic effectiveness of ALL.Method: There were 15 pediatric ALL patients, which had received 50 times of chemotherapy with HD-MTX. The records about blood concentration of MTX and clinical conditions for 50 times chemotherapy were divided into two groups. Group I: contained 25 records of stand-risk patients, administering MTX 3.0g/m2; Group II: contained 25 records of mid and high-risk patients, administering 5.0g/m2. Continuous intravenous dripped MTX for 24th in both two groups, while implemented hydrating and alkalizing for 4 days. All patients were rescued 6 times through leucovorin(LV), 15mg/m~2, since 12th after the end of MTX dripping. Then examined the blood concentration of MTX by fluorescence polarization immunoassay (FPI-A) approach at 24h, 44h, 68h, at the same time inspected liver function, blood routine examination, the occurrence time and degree of toxicological reactions. The relation between pharmacodynamics and toxicology of HD-MTX with statistics approaches.Result: 1) 24h, 44h, 68h blood concentrations of MTX in group I were 30.09±7.04mol/L, 0.39±0.42mol/L, 0.06±0.13mol/L respectively; which in group II were 54.37±11.12mol/L,0.46±0.32mol/L,0.07±0.08mol/L respictively.There was significant difference of blood concentration of MTX between group I and group II at 24h (P< 0.05). 2) There was not significant difference of toxic reaction between both two groups, however, the toxic reaction relates to the blood concentration of MTX. Once the concentration exceeds the safe value (>l.0mol/L at 44h,>0.1mo/L at 68h), the degree and duration of toxic reactions ere heavy.Conclusion: The steady state concentration of MTX will increased will increasing of MTX dose while the occurrence time and degree of toxic reactions relate to toxic concentration. Therefore, it was safety to enhance the dose of MTX depending on credible therapeutic drug monitoring (TDM) value. According to the monitoring value of MTX, we could adjust the dose and time of LV before the occurrence of toxic symptoms so as to reduce the degree of severe and irreversible toxic reactions and ensure the next chemotherapy can be conducted on time. |
PDF Full Text Request