PEDIATRIC GVHD - PHARMACOKINETICS & BIOAVAILABILITY OF IV METHYLPREDNISOLONE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 慢性移植物抗宿主病(CGVHD)可能是异基因骨髓移植的衰弱后果。患有这种疾病的患者可能会累及皮肤、肝脏、胃肠道、肺部和/或眼睛。标准治疗使用免疫抑制药物，如环孢素和类固醇。长期免疫抑制治疗会导致儿童的缺血性坏死、葡萄糖耐量减低、感染、高血压、体重增加、身体习性改变、纹状体、白内障、骨质疏松症、情绪不稳定和生长迟缓。据观察，一些cGVHD患者对口服类固醇有反应，而另一些患者则不起作用，这种观察的原因尚不清楚。这项研究的目的是确定这一组类固醇吸收的病理生理学。受试者将对口服和静脉注射剂量的类固醇进行药代动力学测试，以确定每种给药途径的生物利用度。此外，受试者还将接受测试，以确定是否存在肠道通透性改变，这可能是导致口服类固醇吸收不良的原因之一。为了更好地了解炎症的机制，受试者将进行实验室测试，以确定内皮细胞的炎症水平，这可能是导致口服免疫抑制药物生物利用度降低的原因之一。类固醇吸收、肠道通透性和内皮损伤的机制在这一人群中从未被研究过，因此预期的结果是未知的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic Graft vs. Host Disease (cGVHD) can be a debilitating consequence of allogeneic bone marrow transplantation. Patients who suffer from this condition can have involvement of the skin, liver, gastrointestinal tract, pulmonary system and/or the eyes. The standard treatment utilizes immunosuppressive medications such as cyclosporine and steroids. Treatment with long term immunosuppression can cause avascular necrosis, glucose intolerance, infections, hypertension, weight gain, changes in body habitus, striae, cataracts, osteoporosis, emotional lability, and growth retardation in children. It has been observed that some patients with cGVHD respond to oral steroids while others do not, and the reasons for this observation are unknown. The goal of this study is to determine the pathophysiology of steroid absorption in this group. Subjects will have pharmacokinetic testing done on both oral and intravenous doses of steroids to determine bioavailability from each administration route. In addition, subjects will have tests to determine if there is an alteration in intestinal permeability that may be contributing to poor absorption of oral steroids. To better understand the mechanism of inflammation, subjects will have laboratory tests to determine the level of inflammation in the endothelium that may be contributing to decreased bioavailability of oral immunosupression. The mechanism of steroid absorption, intestinal permeability and endothelial damage have never been studied in this population therefore the expected results are unknown.