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Related Experiment Videos

The postoperative pharmacokinetics of codeine.

K Persson1, M Hammarlund-Udenaes, O Mortimer

  • 1Division of Clinical Pharmacology, Akademiska Sjukhuset, University of Uppsala, Sweden.

European Journal of Clinical Pharmacology
|January 1, 1992
PubMed
Summary

Codeine metabolism and availability vary significantly in patients post-cholecystectomy. Even as extensive metabolizers, morphine levels remain low, suggesting individual differences in codeine

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Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Clinical Pharmacokinetics

Background:

  • Codeine is a widely used analgesic.
  • Its efficacy can be influenced by individual metabolic differences.
  • Post-surgical states may affect drug pharmacokinetics.

Purpose of the Study:

  • To investigate the pharmacokinetics of codeine in patients following cholecystectomy.
  • To assess the systemic availability and metabolism of codeine.
  • To explore the relationship between genetic polymorphism and codeine's metabolic profile.

Main Methods:

  • 12 patients received intravenous and oral codeine doses post-cholecystectomy.
  • Plasma codeine and morphine concentrations were measured.
  • Cytochrome P450 (CYP) 2D6 polymorphism was assessed using dextromethorphan.

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  • Pharmacokinetic parameters including clearance and systemic availability were calculated.

    • Main Results:

    • Codeine exhibited medium to high extraction ratio with significant inter-individual variability in plasma clearance.
    • All patients were extensive metabolizers for CYP2D6.
    • Morphine formation was minimal, with plasma concentrations below detection limits.
    • Systemic availability of codeine showed extensive variation (12-84%).

    Conclusions:

    • Significant inter-individual variability in codeine systemic availability exists post-cholecystectomy.
    • Low morphine formation suggests limited contribution to analgesia via this pathway in this population.
    • Variability in codeine availability may explain differences in analgesic dosage requirements.