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Int. J. Clin. Pract. · Jul 2000
ReviewCodeine analgesia is due to codeine-6-glucuronide, not morphine.
- T B Vree, R T van Dongen, and P M Koopman-Kimenai.
- Institute for Anaesthesiology, Academic Hospital St Radboud, Nijmegen, The Netherlands.
- Int. J. Clin. Pract. 2000 Jul 1; 54 (6): 395-8.
AbstractEighty 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 mu-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.
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