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Species differences in the metabolism of sulphadimethoxine.

ABSTRACT: 1. The fate of sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) was studied in man, rhesus monkey, dog, rat, guinea pig and rabbit. 2. About 20-46% of the dose (0.1g./kg.) of the drug is excreted in the urine in 24hr. in these species, except the rat, in which only 13% is excreted. 3. In man and the monkey sulphadimethoxine N(1)-glucuronide is the major metabolite in the urine. In the rabbit and guinea pig N(4)-acetylsulphadimethoxine is the main metabolite. In the dog the drug is excreted mainly unchanged. In the rat equal amounts of the unchanged drug and its N(4)-acetyl derivative are the main products. 4. Small amounts of sulphadimethoxine N(4)-glucuronide are found in the urine of all the species. Sulphadimethoxine N(1)-glucuronide occurs in small amounts in the urine of rat, dog and guinea pig; none is found in rabbit urine. 5. Sulphadimethoxine N(4)-sulphate was synthesized and found to occur in small amounts in rat urine. 6. Monkey liver homogenates fortified with UDP-glucuronic acid are able to synthesize sulphadimethoxine N(1)-glucuronide with the drug as substrate. Rat liver has also this ability to a slight extent, but rabbit liver is unable to do so. 7. Sulphadimethoxine N(4)-glucuronide is formed spontaneously when the drug is added to human urine. 8. The biliary excretion of the drug and its metabolites was examined in rats. The drug is excreted in rat bile mainly as the N(1)-glucuronide. The N(1)- and N(4)-glucuronides administered as such are extensively excreted in the bile by rats.

SUBMITTER: Bridges JW

PROVIDER: S-EPMC1187037 | biostudies-other | 1968 Oct

REPOSITORIES: biostudies-other

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