The Metabolism of Phenolic Opiates by Rat Intestine

Abstract

1. A range of phenolic opiate agonists and antagonists undergo conjugation during passage across the rat intestine.

2. The efficiency of conjugation, mediated by gut UDP-glucuronyltransferase, is a function of the lipophilicity of the substrate.

3. Conjugation of lipophilic substrates such as buprenorphine and etorphine in rat intestinal mucosa is such that the gut wall must be regarded as the primary site of metabolism of these compounds after oral administration.

4. N-Dealkylation of the N-cyclopropylmethyl opiate, buprenorphine. has been demonstrated in rat gut sacs though dealkylation of N-methyl substrates was not detected.