Metabolism and pharmacokinetics of dihydrocodeine in dog

Abstract

1. 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 549ng/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.