Department of Pathology and Laboratory Medicine, University of British Columbia, Child & Family Research Institute, Vancouver, Canada.
Environ Toxicol Pharmacol. 2009 May;27(3):424-7. doi: 10.1016/j.etap.2008.12.005. Epub 2009 Jan 14.
In metabolomic studies using liquid chromatography mass spectrometry of urine from children with cystic fibrosis (CF), high levels of metabolites of low molecular weight phthalates were found. Phthalate metabolite excretion was explained by therapy with enteric-coated pancreatic enzyme replacements. Phthalate metabolite identity was confirmed by tandem mass spectrometry. Pancreatic insufficient CF children taking Cotazym ECS(®), which is formulated with diethyl phthalate (DEP), had urinary metabolites of DEP. Children taking Creon(®), which has dibutyl phthalate (DBP), excreted DBP metabolites. The estimated concentrations of free MEP were 2-3 orders of magnitude higher than reported from environmental phthalate exposure. Enteric-coated pancreatic enzymes can expose individuals with CF to incessant, high oral intakes of phthalates. Although adverse effects have neither been shown to be present nor absent, we raise the need to consider that individuals requiring life-long therapy with some current pancreatic enzyme replacements chronically ingest high amounts of phthalates.
在对囊性纤维化 (CF) 儿童尿液进行液相色谱-质谱代谢组学研究时，发现了低分子量邻苯二甲酸酯代谢物的高水平。肠溶性胰酶替代治疗可以解释邻苯二甲酸酯代谢物的排泄。通过串联质谱证实了邻苯二甲酸酯代谢物的身份。服用含有邻苯二甲酸二乙酯 (DEP) 的 Cotazym ECS(®) 的胰腺功能不全 CF 儿童，其尿液中存在 DEP 代谢物。服用含有邻苯二甲酸二丁酯 (DBP) 的 Creon(®) 的儿童，其尿液中则排泄 DBP 代谢物。游离 MEP 的估计浓度比环境邻苯二甲酸酯暴露所报道的高出 2-3 个数量级。肠溶性胰酶可使 CF 个体不断暴露于高剂量的口服邻苯二甲酸酯中。尽管尚未显示存在或不存在不良影响，但我们提出需要考虑到，需要终生接受某些目前的胰酶替代治疗的个体，会长期摄入大量的邻苯二甲酸酯。
