Metabolism of arylacetic acids. 3. The metabolic fate of diphenylacetic acid and its variation with species and dose.

1. [carboxy-14C]Diphenylacetic acid has been administered to seven primate species including man, and four other mammals and the qualitative and quantitative aspects of its elimination determined. 2. In most species, 50-100 percent of the administered 14C was excreted in the urine in 48 h; 2-30 percent of the dose was recovered unchanged in the 24 h urine. 3. In all species the only urinary metabolite detected by radiochromatogram scanning was diphenylacetylglucuronide (10-70 percent of dose). Reverse isotope dilution additionally revealed the formation of trace amounts (less than 1 percent of dose) of the glycine conjugate by four species and of the taurine conjugate by the cat. No evidence was found for the formation of a glutamine conjugate. 4. The influence of dose on the pattern of metabolism and excretion of diphenylacetic acid has been studied in the rat. In this species diphenylacetic acid undergoes extensive elimination and enterohepatic circulation.