Abstract
The in-vitro toxicities of sulphametrole and sulphamethoxazole have been compared in three in-vitro tests which involve a rat microsomal metabolite-generating system coupled to either a human mononuclear leucocyte toxicity assay, or a single and two-compartment methaemoglobin-generating assay. Mononuclear leucocyte cell death in the presence of sulphamethoxazole and NADPH was almost doubled, while there was no significant increase in cell death under the same conditions in the presence of sulphametrole. Both compounds formed methaemoglobin in the presence of NADPH, although sulphametrole caused significantly less haemoglobin oxidation (6·7 ± 0·2%) compared with sulphamethoxazole (15·8 ± 8·8%). The sulphonamides formed substantially less methaemoglobin in the two-compartment system, although sulphametrole was again significantly less toxic compared with sulphamethoxazole (1·9 ± 0·2 vs 3·2 ± 0·5%). Future clinical trials may show if sulphametrole is indeed less toxic compared with sulphamethoxazole.
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