Preclinical Toxicity Testing of Co-trimoxazole and Other Trimethoprim/Sulfonamide Combinations

Abstract

The early development of co-trimoxazole, the 1:5 combination of trimethoprim (TMP) and sulfamethoxazole (SMX), was in the late 1950’s and early 1960’s, before much of today’s formalisation of a rigid pattern of toxicity testing of a new medicine. Initial interest lay in co-trimoxazole itself, and in its separate components, trimethoprim and sulfamethoxazole, but there have subsequently been studies of trimethoprim combined with other sulfonamides. It is not surprising, therefore, that the reports of toxicity tests are complex, nor that they are sometimes incomplete according to the standards of the 1980’s, more reliance having been placed on observations in the target species, such as humans and domestic animals, rather than on the contrived circumstances of laboratory experiments.