PEDIATRIC GVHD - PHARMACOKINETICS & BIOAVAILABILITY OF IV METHYLPREDNISOLONE

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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.