Polyethylene glycol safety in children

聚乙二醇对儿童的安全性

• 批准号: 8892324
• 负责人: ROBERT O HEUCKEROTH
• 金额: $ 32.5万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-10 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8892324
• 关键词: Polyethylene; glycol; safety; children

Project Summary/Abstract PEG 3350 is polymeric medicine that is commonly used to treat constipation and for colon cleansing prior to colonoscopy. Although PEG 3350 is only approved by the U.S. FDA for use in people ≥17 years of age for no more than seven days, this medicine is very commonly used in young children, often at adult doses, for months or years at a time. The safety of PEG 3350 use by children or for prolonged periods is not known. Furthermore, although PEG 3350 is a polymer that is poorly absorbed, batches of this medicine tested by the FDA have been found to contain small amounts of low molecular weight compounds (e.g. ethylene glycol and diethylene glycol) that might be absorbed and are known to be toxic in high enough doses. Finally, some families who have given PEG 3350 to their children have reported symptoms to the FDA that they are concerned may have been caused by PEG 3350 ingestion. In particular, there is a concern that PEG 3350 components might cause neurobehavioral symptoms. To address the potential toxicity of PEG 3350 in children (in response RFA-FD-14-088) we plan to develop exceptionally sensitive assays for PEG 3350 components and metabolites thought to be potentially toxic, enroll children, collect biospecimens, collect detailed linked clinical and behavioral data, and analyze serum specimens. Specifically, we will collect serum from children who take PEG 3350 to treat constipation, but who do not have underlying bowel problems or neurobehavioral problems. We will also collect serum from children who have bowel problems that might predispose to increased PEG 3350 component absorption or who have underlying neurological or neurobehavioral problems that might make them more sensitive to PEG 3350 components. We will also collect neurobehavioral data and clinical history for each child, and stool and urine from a subset of children. In addition, we will enroll children who are not taking PEG 3350 in case unexpected metabolites are detected in biospecimens from children who are taking PEG 3350. Sample analysis will be performed using state-of-the-art equipment in the Metabolic Disease Laboratory at our institution, the Children’s Hospital of Philadelphia. As a large pediatric gastroenterology group we have recommended PEG 3350 to many children since this medicine was first approved by the FDA for adult use and we are very interested in working with the FDA to assess the safety of this medicine in children.

项目概要/摘要 PEG 3350 是一种高分子药物，通常用于治疗便秘和术前结肠清洁。 尽管 PEG 3350 仅获得美国 FDA 批准用于 17 岁以上的人群，但没有任何临床意义。 超过 7 天，这种药物在幼儿中非常常用，通常按成人剂量使用数月 儿童或长期使用 PEG 3350 的安全性尚不清楚。 此外，尽管 PEG 3350 是一种吸收性较差的聚合物，但该药物的批次经过了 FDA 已发现含有少量低分子量化合物（例如乙二醇和 二甘醇）可能会被吸收，并且已知在足够高的剂量下会产生毒性。 给孩子服用 PEG 3350 的家庭已向 FDA 报告了他们的症状 担心可能是由摄入 PEG 3350 引起的。特别是，人们担心 PEG 3350。 成分可能会导致神经行为症状 解决 PEG 3350 对儿童的潜在毒性。 （响应 RFA-FD-14-088）我们计划开发针对 PEG 3350 成分的极其灵敏的检测方法 和被认为具有潜在毒性的代谢物，招募儿童，收集生物样本，收集详细的链接 临床和行为数据，并分析血清标本具体来说，我们将从儿童身上收集血清。 服用 PEG 3350 治疗便秘，但没有潜在肠道问题或神经行为问题的人 我们还将收集患有可能易患肠道问题的儿童的血清。 PEG 3350 成分吸收增加或有潜在神经或神经行为问题的人 这可能会使他们对 PEG 3350 成分更加敏感。我们还将收集神经行为数据和 每个孩子的临床病史以及一部分儿童的粪便和尿液 此外，我们还将招募儿童。 不服用 PEG 3350 的儿童，以防在以下儿童的生物样本中检测到意外的代谢物： 正在服用 PEG 3350。样品分析将使用代谢实验室中最先进的设备进行 我们机构费城儿童医院的疾病实验室是一家大型儿科医院。 胃肠病学小组自从该药物首次上市以来，我们已向许多儿童推荐了 PEG 3350 已获得 FDA 批准用于成人，我们非常有兴趣与 FDA 合作评估其安全性 这种药用于儿童。