Studies on the Metabolism of Arylacetic Acids: 5. The Metabolic Fate of 2-Naphthylacetic Acid in the Rat, Rabbit and Ferret

Abstract

1. The fate of [¹⁴C]-2-naphthylacetic acid has been studied in rat, ferret and rabbit and the findings compared with those for the 1-isomer.

2. 2-Naphthylacetic acid was conjugated in all three species with glycine, glutamine, taurine and glucuronic acid.

3. In rat, but not rabbit, 2-naphthylacetic acid is eliminated in the bile (50% dose) and undergoes entergohepatic circulation.

4. The pattern of metabolism and elimination of 2-naphthylacetic acid in rat is dose-dependent. Small doses (5 mg/kg) are excreted in urine and bile mainly as the glucuronic acid conjugate, while larger doses (250 mg/kg) are eliminated in the bile mainly as amino acid conjugates.

5. Metabolic conjugation of 1- and 2-naphthylacetic acids differs in the three species studied. 1-Naphthylacetic acid is conjugated largely with glucuronic acid and amino acid conjugation is minimal, whereas the converse is true of the 2-isomer. These differences in conjugation have been correlated with structural differences between the two acids.

6. 2-Naphthylacetic acid is the first carboxylic acid found to undergo simultaneous amino acid conjugation with glycine, glutamine and taurine in non-primate species. 2-Naphthylacetic acid may be a useful probe for exploring the species occurrence of the various conjugations.