Cumulative nephrotoxicity in patients on long-term platinum (II) chemotherapy is a major clinical problem; successful use of adjuvant platinum chemotherapy requires a solution to this problem. The research proposed herein is designed 1) to develop a new method for the analysis of platinum (II) in plasma and urine; 2) to exploit this method to assess renal handling of platinum (II) in adults under treatment for advanced malignancy having both normal and decreased renal function; 3) to study the organomercurials as competitive blockers of platinum (II) nephrotoxicity both in model chemical systems and in animal models. Platinum (II) analysis is based upon a new high-pressure liquid chromatographic technique. Plasma and urine platinum levels will be obtained for hospitalized patients undergoing chemotherapy and will be compared to other measures of renal function. Kinetic thermodynamic data will be obtained using nuclear magnetic resonance and/or spectroscopic techniques to evaluate competitive binding of organomercurials and platinum (II) complexes to macromolecules. Model studies will be carried out in rats to determine whether organomercurials afford protection against the nephrotoxic effects of cis-dichlorodiamine platinum (II).
NIH ExPorter
NIH ExPorter