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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1989 Nov;28(5):599–604. doi: 10.1111/j.1365-2125.1989.tb03548.x

Morphine metabolism in children.

I A Choonara 1, P McKay 1, R Hain 1, A Rane 1
PMCID: PMC1380022  PMID: 2590614

Abstract

1. The metabolism of morphine was studied in 12 children and nine premature neonates on a continuous infusion of morphine (10-360 micrograms kg-1 h-1). 2. The mean plasma clearance of morphine was significantly higher in children than neonates (25.7 and 4.7 ml min-1 kg-1, respectively) (P less than 0.01). 3. All the neonates and children had detectable concentrations of morphine-3-glucuronide (M3G) in plasma. All the children and five neonates had detectable concentrations of morphine-6-glucuronide (M6G) in plasma or urine. 4. The M3G/morphine ratios in plasma and urine, and M6G/morphine ratios in urine were significantly higher in children than neonates (P less than 0.01), suggesting that morphine glucuronidation capacity is enhanced after the neonatal period. 5. There was no difference in the M3G/M6G ratio in children and neonates, indicating a parallel development of both glucuronidation pathways.

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Selected References

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  1. Aitkenhead A. R., Vater M., Achola K., Cooper C. M., Smith G. Pharmacokinetics of single-dose i.v. morphine in normal volunteers and patients with end-stage renal failure. Br J Anaesth. 1984 Aug;56(8):813–819. doi: 10.1093/bja/56.8.813. [DOI] [PubMed] [Google Scholar]
  2. Aperia A., Broberger O., Elinder G., Herin P., Zetterström R. Postnatal development of renal function in pre-term and full-term infants. Acta Paediatr Scand. 1981 Mar;70(2):183–187. doi: 10.1111/j.1651-2227.1981.tb05539.x. [DOI] [PubMed] [Google Scholar]
  3. Bray R. J. Postoperative analgesia provided by morphine infusion in children. Anaesthesia. 1983 Nov;38(11):1075–1078. doi: 10.1111/j.1365-2044.1983.tb12483.x. [DOI] [PubMed] [Google Scholar]
  4. Chauvin M., Sandouk P., Scherrmann J. M., Farinotti R., Strumza P., Duvaldestin P. Morphine pharmacokinetics in renal failure. Anesthesiology. 1987 Mar;66(3):327–331. doi: 10.1097/00000542-198703000-00011. [DOI] [PubMed] [Google Scholar]
  5. Christensen C. B., Jørgensen L. N. Morphine-6-glucuronide has high affinity for the opioid receptor. Pharmacol Toxicol. 1987 Jan;60(1):75–76. doi: 10.1111/j.1600-0773.1987.tb01724.x. [DOI] [PubMed] [Google Scholar]
  6. Dahlström B., Bolme P., Feychting H., Noack G., Paalzow L. Morphine kinetics in children. Clin Pharmacol Ther. 1979 Sep;26(3):354–365. doi: 10.1002/cpt1979263354. [DOI] [PubMed] [Google Scholar]
  7. Dilworth N. M., MacKellar A. Pain relief for the pediatric surgical patient. J Pediatr Surg. 1987 Mar;22(3):264–266. doi: 10.1016/s0022-3468(87)80343-3. [DOI] [PubMed] [Google Scholar]
  8. Koren G., Butt W., Chinyanga H., Soldin S., Tan Y. K., Pape K. Postoperative morphine infusion in newborn infants: assessment of disposition characteristics and safety. J Pediatr. 1985 Dec;107(6):963–967. doi: 10.1016/s0022-3476(85)80205-5. [DOI] [PubMed] [Google Scholar]
  9. Leslie F. M., Tso S., Hurlbut D. E. Differential appearance of opiate receptor subtypes in neonatal rat brain. Life Sci. 1982 Sep 20;31(12-13):1393–1396. doi: 10.1016/0024-3205(82)90389-7. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Miller R. P., Roberts R. J., Fischer L. J. Acetaminophen elimination kinetics in neonates, children, and adults. Clin Pharmacol Ther. 1976 Mar;19(3):284–294. doi: 10.1002/cpt1976193284. [DOI] [PubMed] [Google Scholar]
  12. Miser A. W., Miser J. S., Clark B. S. Continuous intravenous infusion of morphine sulfate for control of severe pain in children with terminal malignancy. J Pediatr. 1980 May;96(5):930–932. doi: 10.1016/s0022-3476(80)80585-3. [DOI] [PubMed] [Google Scholar]
  13. Nahata M. C., Miser A. W., Miser J. S., Reuning R. H. Variation in morphine pharmacokinetics in children with cancer. Dev Pharmacol Ther. 1985;8(3):182–188. doi: 10.1159/000457035. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Pacifici G. M., Säwe J., Kager L., Rane A. Morphine glucuronidation in human fetal and adult liver. Eur J Clin Pharmacol. 1982;22(6):553–558. doi: 10.1007/BF00609630. [DOI] [PubMed] [Google Scholar]
  16. Rane A., Wilson J. T. Clinical pharmacokinetics in infants and children. Clin Pharmacokinet. 1976;1(1):2–24. doi: 10.2165/00003088-197601010-00002. [DOI] [PubMed] [Google Scholar]
  17. Rollins D. E., von Bahr C., Glaumann H., Moldéus P., Rane A. Acetaminophen: potentially toxic metabolite formed by human fetal and adult liver microsomes and isolated fetal liver cells. Science. 1979 Sep 28;205(4413):1414–1416. doi: 10.1126/science.38505. [DOI] [PubMed] [Google Scholar]
  18. Shimomura K., Kamata O., Ueki S., Ida S., Oguri K. Analgesic effect of morphine glucuronides. Tohoku J Exp Med. 1971 Sep;105(1):45–52. doi: 10.1620/tjem.105.45. [DOI] [PubMed] [Google Scholar]
  19. Svensson J. O., Rane A., Säwe J., Sjöqvist F. Determination of morphine, morphine-3-glucuronide and (tentatively) morphine-6-glucuronide in plasma and urine using ion-pair high-performance liquid chromatography. J Chromatogr. 1982 Jul 9;230(2):427–432. doi: 10.1016/s0378-4347(00)80494-6. [DOI] [PubMed] [Google Scholar]
  20. Säwe J., Kager L., Svensson Eng J. O., Rane A. Oral morphine in cancer patients: in vivo kinetics and in vitro hepatic glucuronidation. Br J Clin Pharmacol. 1985 Apr;19(4):495–501. doi: 10.1111/j.1365-2125.1985.tb02675.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Säwe J., Odar-Cederlöf I. Kinetics of morphine in patients with renal failure. Eur J Clin Pharmacol. 1987;32(4):377–382. doi: 10.1007/BF00543973. [DOI] [PubMed] [Google Scholar]
  22. Säwe J., Svensson J. O., Rane A. Morphine metabolism in cancer patients on increasing oral doses--no evidence for autoinduction or dose-dependence. Br J Clin Pharmacol. 1983 Jul;16(1):85–93. doi: 10.1111/j.1365-2125.1983.tb02148.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tomson G., Lunell N. O., Sundwall A., Rane A. Placental passage of oxazepam and its metabolism in mother and newborn. Clin Pharmacol Ther. 1979 Jan;25(1):74–81. doi: 10.1002/cpt197925174. [DOI] [PubMed] [Google Scholar]
  24. Vandenberghe H., Mac Leod S., Chinyanga H., Endrenyi L., Soldin S. Pharmacokinetics of intravenous morphine in balanced anesthesia: studies in children. Drug Metab Rev. 1983;14(5):887–903. doi: 10.3109/03602538308991414. [DOI] [PubMed] [Google Scholar]

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