Species Differences in the Biotransformation of 4-(2-Methyl-3-(4-chlorobenzoyl)phenyl)butanoic Acid (RU16029)

1. 4-(2-Methyl-3-(4-chlorobenzoyl)phenyl)butanoic acid (RU 16029) is a potent anti-inflammatory and analgesic agent. In humans, its ketone group is rapidly reduced to an alcohol, whereas in rats, mice and dogs, its butanoic sidechain is rapidly oxidized to the corresponding acetic acid. 2. The extent of this oxidation was studied in eleven species. Cats, dogs, rabbits, hens and rodents readily oxidized the side-chain; humans, baboons and pigs showed only weak oxidizing capacity. 3. Species differences were also recorded in the secondary biotransformations. The acetic metabolite is excreted as an acylglucuronide in humans and rats, but as an amide-like conjugate in mice. 4. Comparison with biotransformations undergone by structurally related compounds confirms that the metabolism of a new compound in different species is unpredictable.