摘要
目的分析大剂量甲氨蝶呤（MTX）化疗消除相血药浓度,并探讨其影响因素。方法本研究分析33例ALL患儿,230个疗程,24 h输注大剂量MTX（3 g·m^-2）。检测MTX开始输注第1小时、第6小时、第23小时（稳态血药浓度）和第48小时的血药浓度（C48）;如果C48〉0.40μmol·L^-1,再测第72小时的血药浓度（C72）;以此类推,每24 h测血药浓度1次,直至MTX血药浓度〈0.25μmol·L^-1。结果大剂量MTX化疗后消除相血药浓度不同疗程间差异很大。大多数疗程MTX排泄很快,有201个疗程（占87%）C72〈0.25μmol·L^-1;然而也有少数疗程MTX排泄很慢,有14个疗程（占6%）C96〉0.25μmol·L^-1。不同疗程间C48为0.02～8.86μmol·L^-1,中位数0.20μmol·L^-1。有24个疗程（占10%）C48〉1μmol·L^-1,称为排泄延迟。不同患儿间C48有统计学差异（P=0.000）。导致C48增高的危险因素有男童、化疗前1周内有尿常规异常、化疗前2周内并感染和化疗同时静脉应用头孢曲松（P〈0.05）。导致消除相MTX排泄延迟的危险因素有MTX稳态血药浓度高、MTX总清除率低下和血谷氨酰转移酶升高（P〈0.05）。多种因素二项逻辑回归分析显示,导致MTX消除相排泄延迟的主要危险因素是MTX稳态血药浓度高、化疗前1周内有尿常规异常和化疗前2周内并感染。结论3 g·m^-2 24 h输注大剂量MTX化疗,不同疗程间消除相血药浓度差异很大,多种危险因素导致消除相药物排泄延迟。
Objective To analyze the concentrations of methotrexate（MTX） elimination after high dose infusion and to explore the influencing factors.Methods Thirty-three children with acute lymphoblastic leukemia（ALL） and 230 courses of high-dose MTX 3 g·m^-2 24-hour infusions were included in the study.MTX concentrations at 1 h,6 h,23 h（concentration in steady state） and 48 h（C48） after infusion were measured.If C48〉0.40 μmol·L^-1,MTX concentration at 72 h（C72） after infusion was measured.Sampling was continued every 24 hours until MTX concentration〈0.25 μmol·L^-1.Results There was a wide inter-course variability in MTX concentrations at each sampling time during elimination after high dose infusion.MTX was excreted quickly in most infusions;and there were 201（87%） infusions which C72 were〈0.25 μmol·L^-1.MTX was excreted slowly in a few infusions;and there were 14（6%） infusions which C96〉0.25 μmol·L^-1.There was a wide inter-course variability in C48;the range was 0.02-8.86 μmol·L^-1;and the median was 0.20 μmol·L^-1.There were 24（10%） infusions which C48〉1 μmol·L^-1,and it was defined as ＂delayed＂ MTX elimination.Intra-patient variability in C48 was significant（P=0.000）.Risk factors that correlated with increased C48 of MTX were boys,abnormal urine routine tests within 1 week before infusions,concurrent infections within 2 weeks before infusions,and co-administration of ceftriaxone（P〈0.05）.Risk factors that correlated with delayed MTX elimination were high MTX concentration in steady state,low MTX total clearance,high plasma glutarmyl transferase（P〈0.05）.Binary logistic regression analysis showed that the main risk factors of delayed MTX elimination were high MTX concentration in steady state,abnormal urine routine tests within 1 week before infusions,and concurrent infections within 2 weeks before infusions.Conclusions There is a wide inter-course variability in MTX concentrations at each sampling time during elimination after high-dose MTX 3 g·
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2010年第3期211-214,共4页
Journal of Applied Clinical Pediatrics
