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Codeine disposition in smokers and nonsmokers

J F Rogers, J W Findlay, J H Hull

    Clinical Pharmacology and Therapeutics
    |August 1, 1982
    PubMed
    Summary
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    Smoking does not affect codeine bioavailability or its conversion to morphine. While smokers showed slightly faster clearance, this difference was not clinically significant for codeine metabolism.

    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Clinical Pharmacokinetics

    Background:

    • Codeine is an analgesic prodrug, widely used for pain management.
    • Its efficacy is thought to be partly mediated by its conversion to morphine.
    • Smoking is known to affect drug metabolism, but its impact on codeine is not fully understood.

    Purpose of the Study:

    • To investigate the effect of smoking on codeine bioavailability and its metabolic transformation to morphine.
    • To compare codeine and morphine plasma concentrations in smokers and nonsmokers after oral and intramuscular administration.

    Main Methods:

    • 12 smoking and 11 nonsmoking subjects received single 60 mg doses of codeine intramuscularly and orally, one week apart.
    • Plasma concentrations of codeine and morphine were measured over 12 hours using radioimmunoassay (RIA).

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  • Pharmacokinetic parameters including Cmax, tmax, t1/2, and AUC were analyzed.

    • Main Results:

    • No significant differences were observed between smokers and nonsmokers in codeine Cmax, tmax, t1/2, or AUC for codeine and morphine.
    • Smokers exhibited a faster, though clinically insignificant, mean apparent plasma clearance of codeine after intramuscular injection.
    • Mean oral codeine bioavailability was similar in both groups (smokers: 54.8%, nonsmokers: 50.2%).
    • Higher plasma morphine AUC values were noted after oral administration compared to intramuscular, suggesting first-pass O-demethylation.
    • A subset of subjects showed very low morphine AUC values, indicating inter-individual variability in codeine O-demethylation.

    Conclusions:

    • Smoking does not significantly alter codeine bioavailability or its metabolic conversion to morphine.
    • The observed higher morphine levels after oral codeine do not fully support the hypothesis that codeine's analgesic effects are solely due to its conversion to morphine.
    • Inter-individual differences in codeine O-demethylation exist and may influence analgesic response.