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S R Walker

Publications and source records attributed to S R Walker.

100 records · Page 6Linked to original sources
PubMed1969

Structure and species as factors affecting the metabolism of some methoxy-6-sulphanilamidopyrimidines.

1. A comparative study was made in man, rhesus monkey, rat and rabbit of the urinary excretion of 2-, 4- and 5-methoxy- and 2,4-, 2,5- and 4,5-dimethoxy-6-sulphanilamidopyrimidines given orally. 2. In the rabbit, 70-80% of the dose of each drug was excreted in 2 days, mainly as N(4)-acetyl derivatives, except 2,5-dimethoxy-6-sulphanilamidopyrimidine, which was mainly excreted unchanged. 3. In the rat, 50-70% of the dose of each drug was excreted in 2 days, except the 2-methoxy and 2,4-dimethoxy compounds, whose excretion was about 30%. The N(4)-acetyl derivatives accounted for 20-70% of the drugs excreted, except the 2,5-dimethoxy derivative, which was excreted unchanged. 4. In the rhesus monkey, some 40-60% of the dose of the 2-methoxy, 2,4-dimethoxy and 2,5-dimethoxy compounds was excreted in 2 days, but the 4-methoxy, 5-methoxy and 4,5-dimethoxy compounds were excreted at less than half this rate. The 4-methoxy, 5-methoxy and 4,5-dimethoxy compounds were highly acetylated (80-90%) whereas the 2-methoxy compound was poorly acetylated (17%) and the 2,5-dimethoxy compound hardly at all. The major metabolite of the 2,4-dimethoxy compound in the monkey was the N(1)-glucuronide. 5. In man, 30% of the dose of the 4-methoxy and 2,4-dimethoxy compounds was excreted in 24 hr., whereas the 4,5-dimethoxy compound (Fanasil) was very slowly excreted (12% in 2 days). The 4-methoxy compound was well acetylated (65%), but the 2,4- and 4,5-dimethoxy compounds were not (20-30%). The main metabolite of the 2,4-dimethoxy compound in man was the N(1)-glucuronide. 6. N(1)-Glucuronide formation occurred extensively only with the 2,4-dimethoxy compound and only in man and the rhesus monkey. It did not occur in the rabbit and only to a minor extent in the rat. 7. The 2,5-dimethoxy compound was not significantly acetylated in vivo in the rabbit, rat or monkey, but acetylation occurred in vitro in rabbit or monkey liver homogenates. 8. These findings are discussed.

Animals↗
PubMed1969

Species differences in the metabolism and excretion of sulphasomidine and sulphamethomidine.

1. The excretion of 2,4-dimethyl-6-sulphanilamidopyrimidine (sulphasomidine; Elkosin) and 4-methoxy-2-methyl-6-sulphanilamidopyrimidine (sulphamethomidine) given orally was examined in man, rhesus monkey, rabbit and rat. 2. About 70% of sulphasomidine (0.1g./kg.) is excreted mainly unchanged in the urine by these species in 24hr.; less than 15% of the dose is acetylated and there is no marked species difference in the fate of this drug. 3. Sulphamethomidine is excreted more slowly than sulphasomidine, and in the rat, rabbit and monkey the main metabolite is the N(4)-acetyl derivative. In man, only 20-30% of the dose is excreted in 24hr. and nearly 70% of this is sulphamethomidine N(1)-glucuronide, which is also excreted by the monkey but not by the rat or rabbit. There is therefore a marked species difference in the metabolism of sulphamethomidine. 4. Sulphamethomidine N(1)-glucuronide was synthesized and shown to be identical with the glucuronide isolated from monkey urine. 5. Sulphasomidine, sulphamethomidine and sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) were acetylated by rabbit or monkey liver homogenates. Although sulphasomidine is poorly acetylated in vivo, it is acetylated in vitro at rates comparable with those of the other two drugs. 6. The solubilities, partition coefficients and plasma-protein-binding of the drugs were measured. 7. The results are discussed.

Animals↗
PubMed1968

Species differences in the metabolism of sulphadimethoxine.

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.

Animals↗