SLCO1B1突变致1例甲氨蝶呤清除延迟患儿的药学监护  

The Delayed Excretion of Methotrexate in One Pediatric Patient with SLCO1B1 Mutation

作　　者：湛敏[1] 张洲[1] 李学娟[1] 吴越[1] 魏红[1] 陈泽彬[1] 

机构地区：[1]深圳市儿童医院,广东深圳510038

出　　处：《儿科药学杂志》2016年第9期34-37,共4页Journal of Pediatric Pharmacy

摘　　要：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 influence factors of the delayed excretion of methotrexate（ MTX）,reduce the incidence of adverse reactions. Methods： For a high-risk acute lymphoblastic leukemia（ ALL） children with MTX delayed excretion,gastrointestinal mucosal injury and induced Salmonella typhimurium infection,we analyzed the physiological and pathological factors,the combined medication,and detected the SLCO1B1 polymorphism by sequence in order to explore the related factors influencing the MTX clearance.Results： According to MTX blood drug concentration,the clinical pharmacist believed that the children developed the MTX early-delayed clearance in Block-1 and both early-and late-delayed clearance in Block-2. In combination with related literatures, the clinical pharmacist chose three SNP locuses of SLCO1B1 to explore the effect of genetic polymorphism on MTX clearance. The sequencing results demonstrated that the children had SLCO1B1 c.521,c.1865＋4846 and c.1865＋248 homozygous mutation. The SLOC1B1 mutation and in combined with omeprazole probably contributed to the early-delayed excretion,and the late-delayed excretion was probably contributed by ascites. Conclusion： When using the MTX treating ALL children,the physicians should take physiological,pathological and genetic factors into account. If possible,the related genotype should be detected. Based on the above factors,the physician should determine the reasonable dose of MTX and take necessary precaution. At same time,the medication interfering MTX clearance should be avoided. And eventually the MTX-related adverse event could be reduced.

关 键 词：甲氨蝶呤 清除延迟 SLCO1B1多态性 腹水 

分 类 号：R725.1[医药卫生—儿科]