Pharmacokinetics and metabolism of codeine in humans

Biopharm Drug Dispos. 1992 Aug;13(6):445-60. doi: 10.1002/bdd.2510130607.

Abstract

Codeine (30 mg phosphate) was metabolized by eight human volunteers to the following six metabolites: codeine-6-glucuronide 81.0 +/- 9.3 per cent, norcodeine 2.16 +/- 1.44 per cent, morphine 0.56 +/- 0.39 per cent, morphine-3-glucuronide 2.10 +/- 1.24 per cent, morphine-6-glucuronide 0.80 +/- 0.63 per cent, and normorphine 2.44 +/- 2.42 per cent. Two out of eight volunteers were unable to O-dealkylate codeine into morphine and lack therefore the cytochrome P450 IID6 isoenzyme. The half-life of codeine was 1.47 +/- 0.32 h, that of codeine-6-glucuronide 2.75 +/- 0.79 h, and that of morphine-3-glucuronide 1.71 +/- 0.51 h. The systemic clearance of codeine was 2280 +/- 840 ml min-1, the renal clearance of codeine was 93.8 +/- 29.8 ml min-1, and that of codeine-6-glucuronide was 122 +/- 39.2 ml min-1. The plasma AUC of codeine-6-glucuronide is approximately 10 times higher than that of codeine. Protein binding of codeine and codeine-6-glucuronide in vivo was 56.1 +/- 2.5 per cent and 34.0 +/- 3.6 per cent, respectively. The in vitro protein binding of norcodeine was 23.5 +/- 2.9 per cent; of morphine, 46.5 +/- 2.4 per cent; of normorphine, 23.5 +/- 3.5 per cent; of morphine-3-glucuronide, 27.0 +/- 0.8 per cent; and of morphine-6-glucuronide, 36.7 +/- 3.8 per cent.

MeSH terms

  • Adult
  • Codeine / analogs & derivatives
  • Codeine / metabolism*
  • Codeine / pharmacokinetics
  • Codeine / urine
  • Female
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Morphine / metabolism
  • Morphine Derivatives / metabolism
  • Protein Binding

Substances

  • Morphine Derivatives
  • norcodeine
  • morphine-6-glucuronide
  • Morphine
  • codeine-6-glucuronide
  • morphine-3-glucuronide
  • Codeine