Platinate toxicity: past, present, and prospects.

Using traditional toxicologic methods, four species were studied for their qualitative and quantitative predictiveness of the toxic effects of cis-dichlorodiammineplatinum(II) in man. Of the four species studied, mouse, monkey, rat, and dog, the latter two gave the best overall results. Using an in vivo rat model, it was found that except for chloroplatinic acid, eight of the tested analogs were less nephrotoxic than the parent drug, cis-dichlorodiammineplatinum(II). The in vitro renal toxicity screen using flounder tubules showed that of the 26 compounds studied, about half were less toxic than the parent compound. This in vitro mini-tox system can be performed about 30 times faster and at one fiftieth the cost of the in vivo model. The in vitro studies also provided evidence that the biochemical site of toxicity of platihates is on ATPases. The latter studies suggested a basis for unifying the mechanistic interpretation of the toxic actions on such disparate target organs as the kidney, nerve, stomach, and inner ear.