COMPARATIVE NEPHROTOXICITY OF TETRAPLATIN AND CISPLATIN IN RATS

Cisplatin, a useful therapeutic agent against many forms of cancer, po ssesses significant nephrotoxicity, necessitating a search for agents with similar therapeutic profiles but with less potential for renal da mage. Since tetraplatin, another platinum analog being evaluated in ph ase I clinical trials, has a favorable therapeutic profile when compar ed to cisplatin, we examined the comparative nephrotoxicity of tetrapl atin and cisplatin in rats when both compounds were administered at eq uimolar doses. Based on various parameters, we found that tetraplatin was less nephrotoxic. In vivo injections of equimolar doses of tetrapl atin caused a much lesser rise in serum urea nitrogen and creatinine w hen compared to cisplatin. In vitro, renal slice accumulation of H-3-p -aminohippurate and C-14-tetraethylammonium was significantly decrease d after cisplatin but not after tetraplatin. Morphological damage in t he kidneys was more severe after cisplatin compared to tetraplatin. We conclude through in vivo and in vitro methodology that tetraplatin is significantly less nephrotoxic than cisplatin at comparable therapeut ic doses.