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 N4-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 N4-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 N1-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 N1-glucuronide. 6. N1-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.

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