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Antemortem conversion of codeine to morphine in man

G R Nakamura, E C Griesemer, T T Noguchi

    Journal of Forensic Sciences
    |July 1, 1976
    PubMed
    Summary

    Codeine is metabolized into morphine in the body before death. Bile shows higher morphine levels than codeine, indicating active liver metabolism, while postmortem tissues showed no codeine breakdown.

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    Area of Science:

    • Forensic Toxicology
    • Pharmacokinetics
    • Drug Metabolism

    Background:

    • Codeine is a widely used analgesic and antitussive medication.
    • Understanding codeine's metabolic pathways is crucial for interpreting toxicological findings in overdose cases.
    • Previous studies have suggested codeine can be converted to morphine in the body.

    Purpose of the Study:

    • To investigate the metabolic relationship between codeine and morphine in postmortem drug overdose cases.
    • To determine the extent of codeine to morphine conversion in various biological specimens.
    • To assess the stability of codeine and its metabolites in postmortem tissues under controlled conditions.

    Main Methods:

    • Analysis of codeine and morphine concentrations in blood, bile, liver, kidney, and urine from 45 drug overdose cases.
    • Comparison of codeine to morphine ratios across different biological matrices.
    • In-vitro studies to evaluate codeine demethylation in postmortem tissues stored at cold temperatures.

    Main Results:

    • Evidence of codeine metabolism to morphine was observed in antemortem specimens.
    • Morphine concentrations were generally lower than codeine in blood, liver, kidney, and urine.
    • Bile samples exhibited higher morphine concentrations than codeine, suggesting significant hepatic demethylation.
    • Controlled in-vitro studies confirmed no codeine demethylation in postmortem tissues during 30 days of cold storage.

    Conclusions:

    • Codeine undergoes partial metabolism to morphine in the antemortem stage.
    • The liver plays a significant role in the demethylation of codeine to morphine.
    • Postmortem tissue analysis is reliable for codeine and morphine levels, as cold storage prevents in-vitro demethylation.

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