Abstract
The effect of various combinations of four drugs, isopropylantipyrine, allylisopropylacetylurea, phenacetin, and caffeine, on the acute toxicity in rats was examined. Acute toxicity of a combination of all four in 0.15, 0.06, 0.25, and 0.05 g, respectively, was compared with each of three combinations of these drugs and the following results were obtained. (1) The departure from parallelism of dose-mortality line was not significant except for a group of females given a combination of three drugs excluding isopropylantipyrine. The toxicity was compared by using these dose-mortality lines, and expressed by expreimentally obtained LD50. It was found that the combination of all four drugs was least toxic. (2) The ratio of the predicted LD50 value, which was calculated on the basis of assumption that each component drug would be additively toxic when combined, to the experimentally observed LD50 was used for comparison. The combination of all four drugs gave values of LD50 significantly greater than additive, while the three combinations had LD50 values which were not significantly different from the additive model. (3) Compared with the reference groups treated with phenacetin, etc., alone, the cases in which the abnormal signs were observed in the general conditions and histopathological observations were fewer in the group treated with the combined drug. Particularly the splenic hemosiderin deposit which was induced in the phenacetin group was light in the combination of all four drugs, which seems to show that toxicity of the combined drug is moderate.
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