Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man

Eur J Clin Pharmacol. 1991;41(4):379-82. doi: 10.1007/BF00314972.

Abstract

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 (mumol.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-glucuronide (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / pharmacology*
  • Administration, Oral
  • Adolescent
  • Adult
  • Codeine / administration & dosage
  • Codeine / analogs & derivatives*
  • Codeine / metabolism
  • Codeine / pharmacokinetics*
  • Codeine / urine
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Morphine / metabolism
  • Time Factors

Substances

  • norcodeine
  • Acetaminophen
  • Morphine
  • codeine-6-glucuronide
  • Codeine