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- W1893413863 abstract "In dogs and in a human subject, pyrazinamide was hydrolyzed to pyrazinoic acid. The latter was oxidized to 5-hydroxypyrazinoic acid through the action of xanthine oxidase. A very small fraction of pyrazinoic acid was converted to a compound tentatively identified as pyrazinoylglycine. In addition, pyrazinamide was converted to an unidentified metabolite; this metabolic route does not involve intermediate formation of pyrazinoic acid. When pyrazinoic acid was administered (man, dogs, Cebus monkeys), the major excretory product was 5-hydroxypyrazinoic acid. In addition, unchanged pyrazinoate and sometimes a trace of pyrazinoylglycine appeared in urine. The renal disposition (man, dogs) of pyrazinamide involved filtration and passive reabsorption. Clearance was aporiximately equal to urine flow. In dogs, pyrazinoate was mainly actively reabsorbed by the proximal tubule, but there is evidence consistent with bidirectional transport. In Cebus , bidirectional active transport was easily demonstrable. Hydroxypyrazinoic acid was secreted (man, dogs, Cebus ). In clearance experiments in dogs, massive doses of pyrazinoic acid caused a small uricosuric effect, but in modified stop-flow experiments, inhibition of urate secretion could be demonstrated with small doses. There was no decrease in the effectiveness of pyrazinoate in inhibiting urate secretion when allopurinol was used to prevent formation of 5-hydroxypyrazinoate. In a human subject, pyrazinamide had its characteristic effect (inhibition of urate excretion) even when formation of 5-hydroxypyrazinoate was blocked. The foregoing and the observation that pyrazinoate was produced soon after administration of the amide led to the conclusion that pyrazinoate is the active agent causing urate retention." @default.
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- W1893413863 date "1972-02-01" @default.
- W1893413863 modified "2023-09-29" @default.
- W1893413863 title "Pharmacology of pyrazinamide: metabolic and renal function studies related to the mechanism of drug-induced urate retention." @default.
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