PEDIATRIC GVHD - PHARMACOKINETICS & BIOAVAILABILITY OF IV METHYLPREDNISOLONE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 慢性移植物抗宿主病（cGVHD）可能是异基因骨髓移植的一种使人衰弱的后果。 患有这种病症的患者可能累及皮肤、肝脏、胃肠道、肺系统和/或眼睛。 标准治疗使用免疫抑制药物，如环孢菌素和类固醇。 长期免疫抑制治疗可导致缺血性坏死、葡萄糖耐受不良、感染、高血压、体重增加、体型改变、条纹、白内障、骨质疏松症、情绪不稳定和儿童生长迟缓。 已经观察到，一些cGVHD患者对口服类固醇有反应，而另一些则没有，并且这种观察的原因尚不清楚。 本研究的目的是确定这一组中类固醇吸收的病理生理学。 受试者将接受口服和静脉注射类固醇的药代动力学试验，以确定每种给药途径的生物利用度。 此外，受试者将接受检查，以确定是否存在可能导致口服类固醇吸收不良的肠道通透性改变。 为了更好地理解炎症的机制，受试者将进行实验室检查，以确定可能导致口服免疫抑制剂生物利用度降低的内皮中的炎症水平。 尚未在该人群中研究类固醇吸收、肠渗透性和内皮损伤的机制，因此预期结果未知。

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.