CODEINE ANALGESIA IS DUE TO CODEINE‐6‐GLUCURONIDE, NOT MORPHINE

Abstract

SUMMARY Eighty per cent of codeine is conjugated with glucuronic acid to codeine‐6‐glucuronide. Only 5% of the dose is O‐demethylated to morphine, which in turn is immediately glucuronidated at the 3‐ and 6‐ position and excreted renally. Based on the structural requirement of the opiate molecule for interaction with the μ‐receptor to result in analgesia, codeine‐6‐glucuronide in analogy to morphine‐6‐glucuronide must be the active constituent of codeine. Poor metabolisers of codeine, those who lack the CYP450 2D6 isoenzyme for the O‐demethylation to morphine, experience analgesia from codeine‐6‐glucuronide. Analgesia of codeine does not depend on the formation of morphine and the metaboliser phenotype. ( Int J Clin Pract 2000; 54(6): 395‐398)