Metabolism and excretion of a chromone carboxylic acid (FPL 52757) in various animal species

Abstract

1. The disposition of the chromone carboxylic acid (FPL 52757) in several species has been investigated. The compound is extensively metabolized by hydroxylation in rat, mouse, ferret, squirrel monkey, cynomolgus monkey, rabbit, hamster, stumped-tailed macaque and baboon (e.g. 50–100° in rat, cynomolgus monkey and squirrel monkey). 2. The plasma clearance of the chromone in rat, rabbit and squirrel monkey was 138, 44 and 59 ml/kg per h respectively. Plasma clearance by the dog was slower (13 ml/kg per h) and due mainly to elimination of unchanged compound. 3. As the dog is particularly susceptible to FPL 52757-induced hepatotoxicity the parent compound may be responsible. Species which clear the compound rapidly compared with the dog did not show a hepatotoxic response. 4. Although metabolism occurs in man the clearance is still slow (15 ml/kg per h) and may be one reason for human susceptibility to a mild hepatotoxic effect with the compound.