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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-224 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 elimination phase drug concentration of high dose methotrexate (MTX) chemotherapy and to explore the influencing factors. Methods This study analyzed 33 children with ALL who received 230 courses of therapy and high-dose MTX (3 g.m-2) at 24 h. The first hour, the sixth hour, the 23rd hour (steady state plasma concentration) and the 48th hour plasma concentration (C48) of the MTX began to be detected. If C48> 0.40μmol.L-1, the 72th hour Of plasma concentration (C72); and so on, measured every 24 h blood concentration 1, until the MTX blood concentration <0.25μmol.L-1. Results After the high-dose MTX chemotherapy to eliminate phase drug concentrations vary widely between treatments. However, MTX excretion was slow for a minority of courses, with 14 courses (6%), C96> 0.25μmol.L (87%), C72 <0.25μmol.L-1 -1. C48 was 0.02 ~ 8.86μmol.L-1 and the median was 0.20μmol.L-1 in different courses of treatment. There are 24 courses (10%) C48> 1μmol.L-1, known as excretion delay. There was a significant difference in C48 between children (P = 0.000). The risk factors for elevated C48 were boys, with urinary abnormalities within 1 week prior to chemotherapy, and ceftriaxone (p <0.05) intravenously with infection and chemotherapy within 2 weeks prior to chemotherapy. The risk factors that led to the elimination of phase MTX excretion were high MTX steady-state plasma concentrations, low total MTX clearance, and increased serum glutamyltransferase (P <0.05). Logistic regression analysis of multiple factors showed that the main risk factors that led to the MTX elimination of phase excretion delay were high steady-state plasma concentration of MTX, abnormal urine within 1 week before chemotherapy and infection within 2 weeks before chemotherapy. Conclusions High dose MTX chemotherapy with 3 g.m-224 h infusion can significantly reduce the drug concentration in different courses of treatment, and many kinds of risk factors lead to delayed elimination of drug excretion.