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目的:分析甲氨蝶呤清除延迟的影响因素,使临床更加合理地使用甲氨蝶呤(MTX)、减少不良反应的发生。方法:对1例发生MTX排泄延迟、出现胃肠道黏膜损伤症状并继发鼠伤寒沙门菌感染的急性淋巴细胞性白血病(ALL)高危患儿的生理病理因素、合并用药情况进行分析,并通过测序法分析SLCO1B1多态性,探讨影响MTX清除延迟的相关因素。结果:根据MTX血药浓度,临床药师判断该患儿Block-1时发生了MTX早期清除延迟,Block-2时发生早期和晚期清除延迟。另结合相关文献,临床药师选择SLCO1B1的3个SNP位点进行测序分析,发现患儿为SLCO1B1c.521、c.1865+4846和c.1865+248 3个位点的突变纯合子。SLCO1B1突变和合并使用奥美拉唑可能是导致患儿发生MTX早期清除延迟的原因;腹水可能是导致其发生晚期清除延迟的原因。结论:临床医师在使用MTX治疗ALL患儿时,应综合考虑患儿的生理病理因素和遗传因素等,如有条件,可同时检测相关基因型,根据基因型和肾脏清除率等制定合适的治疗方案或采取一定的预防措施,同时尽量避免选择会导致患儿甲氨蝶呤排泄延迟的相关药物,以减少MTX不良反应的发生。
OBJECTIVE: To analyze the influencing factors of methotrexate clearance delay and make the clinical use of methotrexate (MTX) more reasonable and reduce the incidence of adverse reactions. Methods: One case of high-risk children with acute lymphoblastic leukemia (ALL) with MTX excretion delay, gastrointestinal mucosal injury symptoms and secondary to Salmonella typhimurium infection were analyzed and analyzed Sequencing analysis of SLCO1B1 polymorphism to explore the impact of MTX removal delay related factors. Results: According to the MTX blood concentration, the clinical pharmacist judged the MTX early clearance delay in Block-1 and the early and late clearance delay in Block-2. Combined with the relevant literature, clinical pharmacists choose three SNP sites SLCO1B1 sequencing analysis found that children with SLCO1B1c.521, c.1865 +4846 and c.1865 +24 mutation of the three loci homozygotes. Silencing and combined use of omeprazole for SLCO1B1 may be responsible for the delayed MTX early clearance in children; ascites may account for the delayed debridement. Conclusion: When using MTX to treat children with ALL, clinicians should consider the physiological and pathological factors and genetic factors of children comprehensively. If there are conditions, clinicians can detect the related genotypes at the same time and make appropriate treatment according to genotype and renal clearance rate Program or take some precautionary measures, at the same time try to avoid the selection will lead to delayed release of methotrexate in children related drugs to reduce the incidence of MTX adverse reactions.