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Interindividual and interethnic differences in the demethylation and glucuronidation of codeine (198

Interindividual and interethnic differences in the demethylation and glucuronidation of codeine (198

  1. Jatelka
    Br J Clin Pharmacol 1989 Dec;28(6):629-37

    Yue QY (http://www.drugs-forum.com/sites/en...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Svensson JO (http://www.drugs-forum.com/sites/en...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Alm C (http://www.drugs-forum.com/sites/en...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Sjöqvist F (http://www.drugs-forum.com/sites/en...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Säwe J (http://www.drugs-forum.com/sites/en...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).

    1. The 8 h urinary excretion of codeine and seven of its metabolites was compared in 149 healthy Swedish Caucasians and 133 healthy Chinese following a single oral dose of 25 mg codeine phosphate.

    2. The total 8 h urinary recovery of drug-related material was 74 +/- 24% in the Caucasians and 60 +/- 14% in the Chinese (P less than 0.001). The excretion of unchanged codeine was significantly higher in the Chinese (7.2%) compared with the Caucasians (4.3%, P less than 0.001).

    3. The Caucasians excreted significantly greater proportions of codeine-6-glucuronide (C6G) (62%) than the Chinese (44%) (P less than 0.001). The frequency distribution of the log metabolic ratio (MR) for glucuronidation (codeine/C6G) was shifted towards higher values in the Chinese population. Males in both groups and Chinese smokers had significantly lower glucuronidation MRs than females and non-smokers in the respective populations (P less than 0.001).

    4. The frequency distribution of the MR for O-demethylation (codeine/morphine (M) + M-3 and M-6-glucuronide (M3G and M6G) + normorphine (NM) was highly skewed in the Caucasians, suggestive of a bimodal distribution. There was a 160-fold interindividual variation in this MR. A unimodal distribution of the log O-demethylation MR was observed in Chinese. The Caucasians excreted less M and more M6G than did the Chinese (P less than 0.001).

    5. Significantly more norcodeine (NC) and less NC-glucuronide (NCG) were excreted in the Chinese compared with the Caucasians (P less than 0.001).