The metabolism and pharmacokinetics of dihydrocodeine have been studied in dog. Urinary metabolites after oral administration of dihydrocodeine were identified using hplc with diode-array and ms. 2. In urine, dihydronorcodeine, dihydromorphine and dihydrocodeine glucuronide were identified in comparison with their authentic standards, and dihydronorcodeine 6-glucuronide also appeared to be excreted as a metabolite. 3. The major urinary metabolite was dihydrocodeine glucuronide, recovered as 49% of the dose, and other metabolites were found to be 0.1-3%, 24 h after 3 mg/kg oral administration of dihydrocodeine. Plasma concentrations of unchanged dihydrocodeine were significantly lower after oral rather than intramuscular administration; the maximum concentrations were 40 and 549 ng/ml after oral and intramuscular administration, respectively. This suggests that dihydrocodeine was metabolized via a hepatic first-pass effect after oral administration. 4. Overall, our results indicate that the metabolic pathways of dihydrocodeine in dog were similar to that of codeine metabolism in animals and man.
