Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1992 Jan;33(1):45–49. doi: 10.1111/j.1365-2125.1992.tb03999.x

Infants and young children metabolise codeine to morphine. A study after single and repeated rectal administration.

H Quiding 1, G L Olsson 1, L O Boreus 1, U Bondesson 1
PMCID: PMC1381198  PMID: 1540490

Abstract

1. Codeine was administered rectally to thirteen infants and young children undergoing elective surgery. Nine infants (6-10 months old) received a 4 mg suppository and four children (3-4 years old) an 8 mg suppository. Codeine and its metabolite morphine were measured in plasma by GC/MS. 2. The mean concentrations of codeine at 3, 4 and 5 h after administration were 240, 163 and 123 nmol l-1 in the younger and 309, 251 and 169 nmol l-1 in the older patients. The corresponding concentrations of morphine were 8.3, 7.4 and 4.5 nmol l-1 and 6.8, 5.5 and 2.8 nmol l-1 respectively. One patient in each age group had no detectable amounts of morphine. 3. In the four children, the rectal dose was repeated 6-hourly for four doses. The plasma concentrations of codeine and morphine following the fifth dose were similar to those after the first dose. The mean AUC(0,5 h) of morphine was 1.6% that of codeine. 4. In the infants the mean plasma half-lives of codeine and morphine were 2.6 and 2.5 h. The two infants with the lowest body weights had the longest half-lives. 5. The mean morphine/codeine concentration ratio was 4.3% in the infants and 1.6% in the children, suggesting impaired glucuronidation of morphine in the former group. The hourly concentration ratios were almost identical following the first and fifth dose in the children. 6. We conclude that at the age of 6 months infants are capable of O-demethylating codeine to morphine.

Full text

PDF
45

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chen Z. R., Somogyi A. A., Bochner F. Polymorphic O-demethylation of codeine. Lancet. 1988 Oct 15;2(8616):914–915. doi: 10.1016/s0140-6736(88)92529-9. [DOI] [PubMed] [Google Scholar]
  2. Choonara I. A., McKay P., Hain R., Rane A. Morphine metabolism in children. Br J Clin Pharmacol. 1989 Nov;28(5):599–604. doi: 10.1111/j.1365-2125.1989.tb03548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dayer P., Desmeules J., Leemann T., Striberni R. Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI). Biochem Biophys Res Commun. 1988 Apr 15;152(1):411–416. doi: 10.1016/s0006-291x(88)80729-0. [DOI] [PubMed] [Google Scholar]
  4. Findlay J. W., Butz R. F., Welch R. M. Codeine kinetics as determined by radioimmunoassay. Clin Pharmacol Ther. 1977 Oct;22(4):439–446. doi: 10.1002/cpt1977224439. [DOI] [PubMed] [Google Scholar]
  5. Findlay J. W., Fowle A. S., Butz R. F., Jones E. C., Weatherley B. C., Welch R. M., Posner J. Comparative disposition of codeine and pholcodine in man after single oral doses. Br J Clin Pharmacol. 1986 Jul;22(1):61–71. doi: 10.1111/j.1365-2125.1986.tb02881.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Findlay J. W., Jones E. C., Butz R. F., Welch R. M. Plasma codeine and morphine concentrations after therapeutic oral doses of codeine-containing analgesics. Clin Pharmacol Ther. 1978 Jul;24(1):60–68. doi: 10.1002/cpt197824160. [DOI] [PubMed] [Google Scholar]
  7. Guay D. R., Awni W. M., Halstenson C. E., Findlay J. W., Opsahl J. A., Abraham P. A., Jones E. C., Matzke G. R. Pharmacokinetics of codeine after single- and multiple-oral-dose administration to normal volunteers. J Clin Pharmacol. 1987 Dec;27(12):983–987. doi: 10.1002/j.1552-4604.1987.tb05601.x. [DOI] [PubMed] [Google Scholar]
  8. Hanna M. H., Peat S. J., Woodham M., Knibb A., Fung C. Analgesic efficacy and CSF pharmacokinetics of intrathecal morphine-6-glucuronide: comparison with morphine. Br J Anaesth. 1990 May;64(5):547–550. doi: 10.1093/bja/64.5.547. [DOI] [PubMed] [Google Scholar]
  9. Judis J. Binding of codeine, morphine, and methadone to human serum proteins. J Pharm Sci. 1977 Jun;66(6):802–806. doi: 10.1002/jps.2600660615. [DOI] [PubMed] [Google Scholar]
  10. Kurz H., Mauser-Ganshorn A., Stickel H. H. Differences in the binding of drugs to plasma proteins from newborn and adult man. I. Eur J Clin Pharmacol. 1977 Jul 19;11(6):463–467. doi: 10.1007/BF00562940. [DOI] [PubMed] [Google Scholar]
  11. Lynn A. M., Slattery J. T. Morphine pharmacokinetics in early infancy. Anesthesiology. 1987 Feb;66(2):136–139. doi: 10.1097/00000542-198702000-00005. [DOI] [PubMed] [Google Scholar]
  12. Mortimer O., Persson K., Ladona M. G., Spalding D., Zanger U. M., Meyer U. A., Rane A. Polymorphic formation of morphine from codeine in poor and extensive metabolizers of dextromethorphan: relationship to the presence of immunoidentified cytochrome P-450IID1. Clin Pharmacol Ther. 1990 Jan;47(1):27–35. doi: 10.1038/clpt.1990.4. [DOI] [PubMed] [Google Scholar]
  13. Osborne R., Joel S., Trew D., Slevin M. Analgesic activity of morphine-6-glucuronide. Lancet. 1988 Apr 9;1(8589):828–828. doi: 10.1016/s0140-6736(88)91691-1. [DOI] [PubMed] [Google Scholar]
  14. Quiding H., Anderson P., Bondesson U., Boréus L. O., Hynning P. A. Plasma concentrations of codeine and its metabolite, morphine, after single and repeated oral administration. Eur J Clin Pharmacol. 1986;30(6):673–677. doi: 10.1007/BF00608214. [DOI] [PubMed] [Google Scholar]
  15. Rogers J. F., Findlay J. W., Hull J. H., Butz R. F., Jones E. C., Bustrack J. A., Welch R. M. Codeine disposition in smokers and nonsmokers. Clin Pharmacol Ther. 1982 Aug;32(2):218–227. doi: 10.1038/clpt.1982.151. [DOI] [PubMed] [Google Scholar]
  16. Yue Q. Y., Svensson J. O., Alm C., Sjöqvist F., Säwe J. Codeine O-demethylation co-segregates with polymorphic debrisoquine hydroxylation. Br J Clin Pharmacol. 1989 Dec;28(6):639–645. doi: 10.1111/j.1365-2125.1989.tb03556.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES