Abstract
3,5-Dimethylpyrazole-C14 is absorbed completely from the gastrointestinal tract of fasted rats when administered as an aqueous suspension. Essentially all of the oral dose (95%) is found in the urine within 24 hours. It is converted completely (>99%) to 4 metabolites. Two metabolites, which together with their conjugated forms account for about 98% of the oral dose of 3,5-dimethylpyrazole, have been isolated in crystalline form and their structures determined. In 5 normal, fasted rats the average percentages excreted (± S.D.) as 5-methylpyrazole-3-carboxylic acid and its conjugete form were 13.1 ± 3.8 and 13.6 ± 4.4, respectively. The major metabolite, which was excreted to the extent of 70.8 ± 5.5% in fasted rats, has been unequivocally identified as conjugated 4-hydroxy-3, 5-dimethylpyrazole; it has been isolated from hydrolyzed rat urine in its unconjugated form. An unknown metabolite, which is formed to the extent of 1.3 ± 1.9% of the dose, was not detected in the urine of some of the rats studied.
From the urinary excretion data, the halflife for the appearance of C14 in the urine of the rat was determined to be about 2.4 hours; i.e., about 60% of the C14 is excreted during the first 3 hours.
The fate of 3,5-dimethylpyrazole in fasted rats compared to rats treated with corn oil and SKF-525A indicates that the inhibition of hypoglycemic activity by these agents probably cannot be explained by their effect on the absorption and/or metabolism of 3,5-dimethylpyrazole.
Footnotes
- Accepted June 17, 1965.
- The Williams & Wilkins Comapny
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