The metabolism of sulphamezathine, 4:6-dimethylpyrimidine and 2-amino-4:6-dimethylpyrimidine in the rabbit with observations on the hydroxylation of some other sulphonamides

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Abstract
Sulfa-mezathine (4,b-dimethyl-2-sulfanilamideopyrimidine) is excreted mainly acetylated (79% of the dose). A small amount (9% of dose) is unacetylated, and 12% is excreted apparently conjugated as ether glucuronide. Attempts to isolate the hydroxylation product or glucuronide were unsuccessful. The nature of the hydroxylation product of sulfamezathine is discussed. Examination of glucuronide hydrolysates by paper chromatography provides evidence of the formation of both 5-hydroxy-4,b-dimethyl-2-sulfanilamidopyrimidine and 2-(3[image]-hydroxysulfanilamido)-4,6-dimethylpyrimidine. 4,6-Dimethylpyrimidine is excreted to an extent of 55% as ether-soluble acid. 4-Methylpyridine-6-carboxylic acid was isolated from metabolic urines. A small amt. (8% of the dose) is excreted as ethereal sulfate. 2-Amino-4,6-dimethylpyrimidine is excreted as O-conjugates to an extent of 35% of the dose (13% as ethereal sulfate and 22% as ether glucuronide). 2-Amino-5-hydroxy-4,6-dimethylpyrimidine was isolated from the hydrolyzed urine. There is evidence that hydroxylation in position 3 in the benzene ring occurs to a small extent when sulfadiazine, sulfamerazine, sulfapyrazine, sulfapyr-idine or sulfathiazole are metabolized in the rabbit.
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