Summary
Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly.
After codeine alone, the t1/2 (h), AUC (μmol·l−1·h) and CLR (ml·min−1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively.
For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml·min−1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucoronide (820 codeine alone, 1022 codeine plus paracetamol).
The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.
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Somogyi, A., Bochner, F. & Chen, Z.R. Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man. Eur J Clin Pharmacol 41, 379–382 (1991). https://doi.org/10.1007/BF00314972
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DOI: https://doi.org/10.1007/BF00314972