Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1994 Sep;38(3):271–273. doi: 10.1111/j.1365-2125.1994.tb04352.x

Morphine and morphine-glucuronide concentrations in plasma and CSF during long-term administration of oral morphine.

R T van Dongen 1, B J Crul 1, P M Koopman-Kimenai 1, T B Vree 1
PMCID: PMC1364800  PMID: 7826830

Abstract

Concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured by h.p.l.c. in plasma and cerebrospinal fluid (CSF) samples from 16 patients with cancer receiving oral (controlled-release) morphine. There was a close correlation between plasma and CSF morphine concentrations (r = 0.94, P = 0.0001) and both correlated with drug dosage (r = 0.61, P = 0.013 and r = 0.74, P = 0.0001, respectively). M3G and M6G in plasma and CSF were correlated (r = 0.81 and r = 0.82, both P = 0.0001). No relationship was apparent between M plus M6G concentrations in the CSF and pain scores.

Full text

PDF
271

Selected References

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

  1. Arnér S., Arnér B. Differential effects of epidural morphine in the treatment of cancer-related pain. Acta Anaesthesiol Scand. 1985 Jan;29(1):32–36. doi: 10.1111/j.1399-6576.1985.tb02155.x. [DOI] [PubMed] [Google Scholar]
  2. Bigler D., Christensen C. B., Eriksen J., Jensen N. H. Morphine, morphine-6-glucuronide and morphine-3-glucuronide concentrations in plasma and cerebrospinal fluid during long-term high-dose intrathecal morphine administration. Pain. 1990 Apr;41(1):15–18. doi: 10.1016/0304-3959(90)91103-P. [DOI] [PubMed] [Google Scholar]
  3. Carrupt P. A., Testa B., Bechalany A., el Tayar N., Descas P., Perrissoud D. Morphine 6-glucuronide and morphine 3-glucuronide as molecular chameleons with unexpected lipophilicity. J Med Chem. 1991 Apr;34(4):1272–1275. doi: 10.1021/jm00108a005. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Khojasteh A., Evans W., Reynolds R. D., Thomas G., Savarese J. J. Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation. J Clin Oncol. 1987 Jun;5(6):956–961. doi: 10.1200/JCO.1987.5.6.956. [DOI] [PubMed] [Google Scholar]
  6. Koopman-Kimenai P. M., Vree T. B., Cress-Tijhuis M. W., Booy L. H., Drijkoningen G. High-performance liquid chromatography and preliminary pharmacokinetics of nicomorphine and its metabolites 3-nicotinoyl- and 6-nicotinoylmorphine and morphine. J Chromatogr. 1987 May 15;416(2):382–387. doi: 10.1016/0378-4347(87)80524-8. [DOI] [PubMed] [Google Scholar]
  7. McQuay H. J., Carroll D., Faura C. C., Gavaghan D. J., Hand C. W., Moore R. A. Oral morphine in cancer pain: influences on morphine and metabolite concentration. Clin Pharmacol Ther. 1990 Sep;48(3):236–244. doi: 10.1038/clpt.1990.145. [DOI] [PubMed] [Google Scholar]
  8. Milne R. W., Nation R. L., Somogyi A. A., Bochner F., Griggs W. M. The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive-care patients. Br J Clin Pharmacol. 1992 Jul;34(1):53–59. doi: 10.1111/j.1365-2125.1992.tb04107.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Osborne R., Joel S., Trew D., Slevin M. Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Clin Pharmacol Ther. 1990 Jan;47(1):12–19. doi: 10.1038/clpt.1990.2. [DOI] [PubMed] [Google Scholar]
  10. Poulain P., Ribon A. M., Hanks G. W., Hoskin P. J., Aherne G. W., Chapman D. J. CSF concentrations of morphine-6-glucuronide after oral administration of morphine. Pain. 1990 Apr;41(1):115–116. doi: 10.1016/0304-3959(90)91116-Z. [DOI] [PubMed] [Google Scholar]
  11. Samuelsson H., Hedner T., Venn R., Michalkiewicz A. CSF and plasma concentrations of morphine and morphine glucuronides in cancer patients receiving epidural morphine. Pain. 1993 Feb;52(2):179–185. doi: 10.1016/0304-3959(93)90129-D. [DOI] [PubMed] [Google Scholar]
  12. Somogyi A. A., Nation R. L., Olweny C., Tsirgiotis P., van Crugten J., Milne R. W., Cleary J. F., Danz C., Bochner F. Plasma concentrations and renal clearance of morphine, morphine-3-glucuronide and morphine-6-glucuronide in cancer patients receiving morphine. Clin Pharmacokinet. 1993 May;24(5):413–420. doi: 10.2165/00003088-199324050-00005. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Wahlström A., Winblad B., Bixo M., Rane A. Human brain metabolism of morphine and naloxone. Pain. 1988 Nov;35(2):121–127. doi: 10.1016/0304-3959(88)90219-9. [DOI] [PubMed] [Google Scholar]

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

RESOURCES