Metabolism of Arylacetic Acids: 1. The Fate of 1-Naphthylacetic Acid and its Variation with Species and Dose

Abstract

1. [carboxy-¹⁴C]-1-Naphthylacetic acid has been administered to man, 6 primate species and 4 other mammalian species and the urinary metabolites examined by radiochromatogram scanning and reverse isotope dilution. Animals all received a dose of 100 mg/kg and man received 5 mg, orally.

2. Most species excreted at least 60% of the ¹⁴C dose in the urine in 48 h. Unchanged acid was a minor (0-17% dose) excretion product in all species except the cynomolgus monkey (35%).

3. In man, in 24 h 95% of ¹⁴C was excreted as 1 -naphthylacetyl-glucuronide and 5% as 1-naphthylacetyltaurine.

4. 1-Naphthylacetylglucuronide was the major excretion product in all species except the bushbaby (21% dose) and the cat, which did not form this conjugate.

5. 1-Naphthylacetylglutamine was formed only by the cynomolgus, squirrel and capuchin monkeys and marmoset, and in no case accounted for more than 3% dose.

6. 1-Naphthylacetylglycine was found in the urines of 4 primate and 3 non-primate species, and was the major metabolite in the squirrel monkey, bushbaby and cat.

7. 1-Naphthylacetyltaurine was excreted by all species except the rabbit and the fruit bat. It was a major excretion product in the squirrel and capuchin monkeys, the marmoset and the cat.

8. The influence of dose on the pattern of metabolism and excretion of 1-naphthylacetic acid has been investigated in the rat.