The pharmacokinetics and metabolism of 4-aminopropiophenone (PAPP), a cyanide antidote, have been studied in rats, dogs and cynomolgus monkeys using 14C-PAPP. Radiolabelled material was rapidly excreted in all three species, mainly in urine. In rats, PAPP was metabolized by N-acetylation, while in dogs, ring and aliphatic hydroxylation occurred. In monkeys, both N-acetylation and oxidation took place. In the latter pathway, PAPP was oxidized to p-aminobenzoic acid which underwent amino acid-conjugation to p-aminohippuric acid. In rat blood in vitro, the PAPP metabolites, p-aminobenzoic, p-aminohippuric and N-acetyl-p-aminobenzoic acid were only weak methaemoglobin producers.
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