The Conjugation of 4-Chloro- and 4-Nitro-phenylacetic Acids in Man, Monkey and Rat

Abstract

1. The conjugation of 4-chloro- and 4-nitro-phenylacetic acid in man, rhesus monkey, capuchin monkey and the rat has been investigated.

2. The four species excreted up to 95% of the radioactivity from an oral or injected dose of [¹⁴C]-4-chlorophenylacetic acid in the urine in 24 h. The major conjugate in the urine of a human subject after oral dosing, and the rhesus and capuchin monkeys after intramuscular injection, was 4-chlorophenacetyl-glutamine. The two monkeys, but not man, excreted also small amounts (<1% dose) of 4-chlorophenacetylglycine. The rat, however, excreted over 90% of the dose after intraperitoneal injection as the glycine conjugate and no glutamine derivative was detected. The rhesus and capuchin monkeys also excreted considerable amounts (up to 30% dose) of the acid unchanged.

3. The pattern of conjugation of 4-chlorophenylacetic acid in these four species is similar to that found for phenylacetic acid itself (James et al., 1972).

4. [¹⁴C]-4-Nitrophenylacetic acid was rapidly excreted in the urine (90% dose in 24 h) by humans (after oral administration), and by rhesus monkeys and rats (after intraperitoneal injection). Man and the rhesus monkey excreted most (about 80% dose) of the acid unchanged together with small amounts (5–8% dose) of an unidentified metabolite which gave 4-nitrophenylacetic acid on acid hydrolysis. The rat, however, excreted 61% of the dose as 4-nitrophenacetylglycine and 28% unchanged.