It is proposed to test in animal models the potential efficacy of administration of bucillamine a potent antioxidant and immunomodulating agent for prevention of radiocontrast-induced nephropathy. Both intravenous and oral administration of bucillaminewill be investigated in two separate rat models relevant to clinical radiocontrast-induced worsening of renal disease. One is a model of acute tubular necrosis due to transient ischemia by clamping the renal pedicals and the other is a model of radio contrast-induced renal necrosis following pretreatment with a nitric oxide inhibitor. Bucillamine has been effective in reducing cardiac, liver or lung injury due to oxidative or reperfusion stress in animal models. Renal injury due to contrast agents has considerable similarity to these settings in that it also appears to be related to transient ischemia and oxidative stress. Bucillamine has been demonstrated to be safe in normal humans with intravenous administration in Phase I studies and has been a successful oral treatment for rheumatoid arthritis in foreign markets. Keystone Biomedical has patent protection for use of bucillamine in oxidative and reperfusion injury. Use of radiocontrast agents for clinical diagnostic tests in patients with renal abnormalities is frequently necessary but is associated with a risk of worsening the renal impairment. There is an urgent need for a treatment to reduce the risk of worsening renal disease due to radiocontrast exposure. A successful treatment would garner a very large market in the U.S. and abroad. If the proposed studies are successful the applicant will apply for funds for Phase II studies to confirm proof of principle of this treatment in humans and to assess optimal dosing. Subsequently commercial funding for Phase III studies aimed at gaining sufficient verification of efficacy to acquire markeing approval through the Food and Drug Administration will be sought.
Thesaurus Terms: acute renal failure, antioxidant, chemoprevention, contrast media, diagnosis procedure safety, drug screening /evaluation, immunomodulator, kidney disorder chemotherapy, kidney imaging /visualization, kidney necrosis, nonhuman therapy evaluation, renal toxin, therapy design /development creatinine, cytokine, disease /disorder model, drug adverse effect, iatrogenic disease, kidney disorder diagnosis, kidney pharmacology, oxidative stress, oxidoreductase inhibitor, pharmacokinetics, renal ischemia /hypoxia bioimaging /biomedical imaging, histopathology, laboratory rat
