SPECIES-DIFFERENCES IN METABOLISM OF CODEINE - URINARY-EXCRETION OF CODEINE GLUCURONIDE, MORPHINE-3-GLUCURONIDE AND MORPHINE-6-GLUCURONIDE IN MICE, RATS, GUINEA-PIGS AND RABBITS

1. Metabolites of codeine were determined by use of h.p.l.c. in urine of male mice, rats, guinea pigs and rabbits injected with 10mg codeine/kg subcutaneously. 2. In 24 h urines of these species, unchanged codeine, codeine glucuronide, free morphine, and morphine-3-glucuronide were as follows: mice, 6.8,1.6, 0.8 and 7.6% dose; rats, 1.6, 0.2, 4.3 and 23.9% dose; guinea pigs, 1.6, 39.8, 0.2 and 1.6% dose; rabbits, 2.2, 24.5, 1.3 and 17.9% dose. Urinary excretion of morphine-6-glucuronide was 0.7% dose in guinea pigs, 1.9% in rabbits, and not detectable in mice and rats. Norcodeine was found only in the urine of mice. 3. These results indicate that codeine is metabolized in all four species by glucuronid-ation and by oxidative N- and O-demethylation, but the quantitative excretions of metabolites were quite different in different species. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.