| Objective: The plasma concentrations of methotrexate in patients with non-Hodgkin lymphoma(NHL)were monitored by Liquid Chromatography Mass Spectrometry/Mass Spectrometry(LC-MS/MS),and the factors affecting the plasma concentration of methotrexate(MTX)were analyzed.The correlation between the plasma concentration of methotrexate and its side effects,so as to provide the basis for rational application of methotrexate in the clinical practice were studied.Methods: From January 2016 to December 2016,38 cases in the fourth hospital of Hebei Medical University underwent HD-MTX treatment of NHL patients,a total of 60 cases,aged 2 to 67 years old,38 male patients,22 female patients were enrolled.The dosage of HD-MTX was 1-5g/m2,and the dosage of MTX was continuous intravenous infusion of 24 h.During the 3 days after the drug administration,the patients were treated with full hydration and alkalization of urine,and calcium folinate(CF)was administered after instillation of methotrexate for about 36 h.The initial rescue dose was 15 mg/m2,intravenous injection every 6h,and the specific rescue dose and frequency were adjusted according to the concentration of methotrexate.LC-MS/MS was used to determine the plasm concentration of MTX after 44 h HD-MTX treatment,methotrexate(C44h)more than 1.0 μmol·L-1 for the elimination delay group,methotrexate(C44h)Less than equal to 1.0 μmol·L-1 for the normal group,the normal excretion were 56 cases,4 cases of delayed excretion group.1 The age,body mass index(BMI),MTX dose were recorded,independent samples t-test and multiple linear regression analysis were used to analyze the correlation of gender,age,BMI value,MTX dosage and methotrexate concentration((C44h).2 Serum creatinine clearance(44h)after treatment was recorded and the correlation between creatinine clearance(Ccr)and methotrexate concentration(C44h)was analyzed.3 The side effects of 1-7d on bone marrow suppression,abnormal liver function,abnormal renal function,gastrointestinal reaction,mucosal damage,skin rash,secondary infection and other side effects of HD-MTX were recorded.Adverse reactions were classified into grade I to IV according to NCI classification standard for common toxicity.To compare the correlation between MTX normal excretion group and delayed excretion group and the incidence of adverse reactions.Results: 1 Independent univariate analysis revealed that Methotrexate concentration(C44h)was positively correlated with age,MTX dose,and BMI(P<0.05),but not with gender.Multiple linear regression analysis revealed that the age,MTX dose were the significantly independent factors with C44 h.2 The delayed excretion rate of C44 h was 13.3%.The difference of methotrexate concentration(C44h)between normal renal function group and impaired renal function group after treatment was statistically significant(P<0.05).3 MTX adverse reaction rates were myelosuppression(68.3%),gastrointe stinal reactions(40.0%),secondary infection(33.3%),abnormal liver function(33.3%),mucosal toxicity(30%),abnormal renal function(20.0%)rash mucosal damage(11.7%).4 The rate of delayed excretion toxicity group is higher than the normal group,the renal toxicity was significantly different(P<0.05).And secondary infection,bone marrow suppression,gastrointestinal reactions,abnormal liver function,mucosal injury,the incidence of rashes were no significant difference between the two groups(P>0.05).Conclusion: 1 The age of patients and HD-MTX dosage were the significantly independent factors with methotrexate concentration(C44h).2 There was a significant correlation between Ccr and(C44h)in patients with normal renal function after treatment with methotrexate.It is suggested that renal function is still one of the main factors affecting the excretion of methotrexate.3 Methotrexate concentration(C44h)monitoring can be used to predict the excretion delay of MTX effectively,and to provide a reasonable basis for the clinical application of methotrexate and the development of calcium leucovorin rescue program. |
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