The fate of sulphadimethoxine in primates compared with other species

Abstract

1. The metabolism of sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) was examined in nine species of primates and nine species of non-primates. 2. The main metabolite of the drug in the urine in man, rhesus monkey, baboon, squirrel monkey, capuchin, bushbaby, slow loris and tree shrew was sulphadimethoxine N1-glucuronide. In the green monkey, although the main metabolite was N4-acetylsulphadimethoxine, the N1-glucuronide was also a major metabolite. 3. In the dog, rat, mouse, guinea pig, Indian fruit bat and hen the N1-glucuronide was a minor metabolite in the urine, whereas in the cat, ferret and rabbit this glucuronide was not found in the urine. 4. All the species examined except the dog excreted some N4-acetylsulphadimethoxine, which was the major metabolite in the green monkey, rabbit and guinea pig. 5. In the tree shrew, a doubtful primate, N1-glucuronide formation was similar to that in the other primates. 6. It is suggested that the slow excretion of the drug by the rat may be due partly to strong binding of the drug to tissue proteins and that the strength of binding may vary with species. 7. In the rat the amount of N1-glucuronide found in the urine is not a true indication of the extent of this conjugation since much more of the conjugate was found in the bile (7% of the dose) than in the urine (1%). In the rabbit, no N1-glucuronide was found in the bile or urine, but a small amount of sulphadimethoxine N4-glucuronide was found in the bile of the rat (0.5% of dose) and rabbit (0.8%).