Relationships between plasma concentrations of morphine, morphine-3-glucuronide, morphine-6-glucuronide, and intravenous morphine titration outcomes in the postoperative period

Fundamental and Clinical Pharmacology

Volumn 25, Issue 4, 2011, Pages 518-527

  Hammoud, Hala Abou ^a   Aymard, Guy ^a   Lechat, Philippe ^a   Boccheciampe, Nicolas ^a   Riou, Bruno ^a   Aubrun, Frédéric ^a  

^a SORBONNE UNIVERSITÉ   (France)

Author keywords

Intravenous morphine; Plasma dosage; Titration in PACU

Indexed keywords

MORPHINE; MORPHINE 3 GLUCURONIDE; MORPHINE 6 GLUCURONIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PARACETAMOL;

ADULT; ANALGESIA; ARTICLE; BLOOD SAMPLING; DRUG BLOOD LEVEL; DRUG ERUPTION; DRUG HYPERSENSITIVITY; FEMALE; HUMAN; HYPOTENSION; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; OXYGEN THERAPY; PATIENT MONITORING; POSTOPERATIVE PAIN; POSTOPERATIVE PERIOD; PRIORITY JOURNAL; PRURITUS; RECOVERY ROOM; SEDATION; VISUAL ANALOG SCALE; VOMITING;

AGE FACTORS; AGED; FEMALE; HUMANS; INJECTIONS, INTRAVENOUS; MALE; MIDDLE AGED; MORPHINE; MORPHINE DERIVATIVES; OBESITY; PAIN MEASUREMENT; PAIN, POSTOPERATIVE; POSTOPERATIVE CARE; SEX CHARACTERISTICS; TREATMENT FAILURE; TREATMENT OUTCOME;

EID: 79959941068     PISSN: 07673981     EISSN: 14728206     Source Type: Journal    
DOI: 10.1111/j.1472-8206.2010.00867.x     Document Type: Article

References (53)

1. Upton R.N., Semple T.J., Macintyre P.E. Pharmacokinetic optimisation of opioid treatment in acute pain therapy. Clin. Pharmacokinet. (1997) 33 225-244.
2. Aubrun F., Monsel S., Langeron O., Coriat P., Riou B. Postoperative titration of intravenous morphine. Eur. J. Anaesthesiol. (2001) 18 159-165.
3. Aubrun F., Salvi N., Coriat P., Riou B. Sex- and age-related differences in morphine requirements for postoperative pain relief. Anesthesiology (2005) 103 156-160.
4. Aubrun F., Monsel S., Langeron O., Coriat P., Riou B. Postoperative titration of intravenous morphine in the elderly patient. Anesthesiology (2002) 96 17-23.
5. Chen Z.R., Irvine R.J., Somogyi A.A., Bochner F. Mu receptor binding of some commonly used opioids and their metabolites. Life Sci. (1991) 48 2165-2171.
6. Romberg R., Olofsen E., Sarton E., den Hartigh J., Taschner P.E., Dahan A. Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers: absence of sex differences. Anesthesiology (2004) 100 120-133.
7. Skarke C., Darimont J., Schmidt H., Geisslinger G., Lotsch J. Analgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers. Clin. Pharmacol. Ther. (2003) 73 107-121.
8. Lotsch J., Kobal G., Geisslinger G. No contribution of morphine-6-glucuronide to clinical morphine effects after short-term administration. Clin. Neuropharmacol. (1998) 21 351-354.
9. Lotsch J., Zimmermann M., Darimont J. et al. Does the A118G polymorphism at the mu-opioid receptor gene protect against morphine-6-glucuronide toxicity? Anesthesiology (2002) 97 814-819.
10. Milne R.W., Nation R.L., Somogyi A.A. The disposition of morphine and its 3- and 6-glucuronide metabolites in humans and animals, and the importance of the metabolites to the pharmacological effects of morphine. Drug Metab. Rev. (1996) 28 345-472.
11. Bartlett S.E., Cramond T., Smith M.T. The excitatory effects of morphine-3-glucuronide are attenuated by LY274614, a competitive NMDA receptor antagonist, and by midazolam, an agonist at the benzodiazepine site on the GABAA receptor complex. Life Sci. (1994) 54 6876-6894.
12. Halliday A.J., Bartlett S.E., Colditz P., Smith M.T. Brain region-specific studies of the excitatory behavioral effects of morphine-3-glucuronide. Life Sci. (1999) 65 225-236.
13. Smith M.T. Neuroexcitatory effects of morphine and hydromorphone: evidence implicating the 3-glucuronide metabolites. Clin. Exp. Pharmacol. Physiol. (2000) 27 524-528.
14. Ouellet D.M., Pollack G.M. Effect of prior morphine-3-glucuronide exposure on morphine disposition and antinociception. Biochem. Pharmacol. (1997) 53 1451-1457.
15. Penson R.T., Joel S.P., Bakhshi K., Clark S.J., Langford R.M., Slevin M.L. Randomized placebo-controlled trial of the activity of the morphine glucuronides. Clin. Pharmacol. Ther. (2000) 68 667-676.
16. Penson R.T., Joel S.P., Clark S., Gloyne A., Slevin M.L. Limited phase I study of morphine-3-glucuronide. J. Pharm. Sci. (2001) 90 1810-1816.
17. Andersen G., Christrup L., Sjogren P. Relationships among morphine metabolism, pain and side effects during long-term treatment: an update. J. Pain Symptom Manage. (2003) 25 74-91.
18. Quigley C., Joel S., Patel N., Baksh A., Slevin M. Plasma concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide and their relationship with analgesia and side effects in patients with cancer-related pain. Palliat. Med. (2003) 17 185-190.
19. Klepstad P., Borchgrevink P.C., Dale O. et al. Routine drug monitoring of serum concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide do not predict clinical observations in cancer patients. Palliat. Med. (2003) 17 679-687.
20. Faura C.C., Collins S.L., Moore R.A., McQuay H.J. Systematic review of factors affecting the ratios of morphine and its major metabolites. Pain (1998) 74 43-53.
21. Lugo R.A., Kern S.E. Clinical pharmacokinetics of morphine. J. Pain Palliat. Care Pharmacother. (2002) 16 5-18.
22. Consensus conference. Management of postoperative pain in adults and children. Ann. Fr. Anesth. Réanim. (1998) 17 445-461.
23. DeLoach L.J., Higgins M.S., Caplan A.B., Stiff J.L. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth. Analg. (1998) 86 102-106.
24. Aubrun F., Langeron O., Quesnel C., Coriat P., Riou B. Relationships between measurement of pain using visual analog score and morphine requirements during postoperative intravenous morphine titration. Anesthesiology (2003) 98 1415-1421.
25. Ramsay M.A., Savege T.M., Simpson B.R., Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br. Med. J. (1974) 2 656-659.
26. Wright A.W., Smith M.T. Improved one-step solid-phase extraction method for morphine, morphine-3-glucuronide, and morphine-6-glucuronide from plasma and quantitation using high-performance liquid chromatography with electrochemical detection. Ther. Drug Monit. (1998) 20 215-218.
27. Meng Q.C., Cepeda M.S., Kramer T., Zou H., Matoka D.J., Farrar J. High-performance liquid chromatographic determination of morphine and its 3- and 6-glucuronide metabolites by two-step solid-phase extraction. J. Chromatogr. B Biomed. Sci. Appl. (2000) 742 115-123.
28. Ary K., Rona K. LC determination of morphine and morphine glucuronides in human plasma by coulometric and UV detection. J. Pharm. Biomed. Anal. (2001) 26 179-187.
29. Aubrun F., Bunge D., Langeron O., Saillant G., Coriat P., Riou B. Postoperative morphine consumption in the elderly patient. Anesthesiology (2003) 99 160-165.
30. 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) 47 12-19.
31. Lotsch J., Skarke C., Geisslinger G., Lotsch J. Morphine metabolites as novel analgesic drugs? Curr. Opin. Anaesthesiol. (2004) 17 449-453.
32. Lotsch J. Opioid metabolites. J. Pain Symptom Manage. (2005) 29 S10-S24.
33. Wittwer E., Kern S.E. Role of morphine's metabolites in analgesia: concepts and controversies. AAPS J. (2006) 8 E348-E352.
34. Coller J.K., Christrup L.L., Somogyi A.A. Role of active metabolites in the use of opioids. Eur. J. Clin. Pharmacol. (2009) 65 121-139.
35. Bickel U., Schumacher O.P., Kang Y.S., Voigt K. Poor permeability of morphine 3-glucuronide and morphine 6-glucuronide through the blood-brain barrier in the rat. J. Pharmacol. Exp. Ther. (1996) 278 107-113.
36. Lotsch J., Skarke C., Schmidt H., Grosch S., Geisslinger G. The transfer half-life of morphine-6-glucuronide from plasma to effect site assessed by pupil size measurement in healthy volunteers. Anesthesiology (2001) 95 1329-1338.
37. Dale O., Thoner J., Nilsen T., Tveita T., Borchgrevink P.C., Klepstad P. Serum and cerebrospinal fluid morphine pharmacokinetics after single doses of intravenous and intramuscular morphine after hip replacement surgery. Eur. J. Clin. Pharmacol. (2007) 63 837-842.
38. Lotsch J., Kobal G., Stockmann A., Brune K., Geisslinger G. Lack of analgesic activity of morphine-6-glucuronide after short-term intravenous administration in healthy volunteers. Anesthesiology (1997) 87 1348-1358.
39. Motamed C., Mazoit X., Ghanouchi K. et al. Preemptive intravenous morphine-6-glucuronide is ineffective for postoperative pain relief. Anesthesiology (2000) 92 355-360.
40. Mazoit J.X., Butscher K., Samii K. Morphine in postoperative patients: pharmacokinetics and pharmacodynamics of metabolites. Anesth. Analg. (2007) 105 70-78.
41. Paqueron X., Lumbroso A., Mergoni P. et al. Is morphine-induced sedation synonymous with analgesia during intravenous morphine titration? Br. J. Anaesth. (2002) 89 697-701.
42. Lentschener C., Tostivint P., White P.F., Gentili M.E., Ozier Y. Opioid-induced sedation in the postanesthesia care unit does not insure adequate pain relief: a case-control study. Anesth. Analg. (2007) 105 1143-1147.
43. Hasselstrom J., Berg U., Lofgren A., Sawe J. Long lasting respiratory depression induced by morphine-6-glucuronide? Br. J. Clin. Pharmacol. (1989) 27 515-518.
44. Lipkowski A.W., Carr D.B., Langlade A., Osgood P.F., Szyfelbein S.K. Morphine-3-glucuronide: silent regulator of morphine actions. Life Sci. (1994) 55 149-154.
45. Gardmark M., Karlsson M.O., Jonsson F., Hammarlund-Udenaes M. Morphine-3-glucuronide has a minor effect on morphine antinociception. Pharmacodynamic modeling. J. Pharm. Sci. (1998) 87 813-820.
46. Ashby M., Fleming B., Wood M., Somogyi A. Plasma morphine and glucuronide (M3G and M6G) concentrations in hospice inpatients. J. Pain Symptom Manage. (1997) 14 157-167.
47. Mao J.. Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy. Pain (2002), 100, 213-217.
48. Simonnet G., Rivat C. Opioid-induced hyperalgesia: abnormal or normal pain? Neuroreport (2003) 14 1-7.
49. Ossipov M.H., Lai J., King T. et al. Antinociceptive and nociceptive actions of opioids. J. Neurobiol. (2004) 61 126-148.
50. Skarke C., Geisslinger G., Lotsch J. Is morphine-3-glucuronide of therapeutic relevance? Pain (2005) 116 177-180.
51. van Dorp E.L., Kest B., Kowalczyk W.J. et al. Morphine-6ß-glucuronide rapidly increases pain sensitivity independently of opioid receptor activity in mice and humans. Anesthesiology (2009) 110 1356-1363.
52. Lotsch J., Skarke C., Liefhold J., Geisslinger G. Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives. Clin. Pharmacokinet. (2004) 43 983-1013.
53. Landau R., Cahana A., Smiley R.M., Antonarakis S.E., Blouin J.L. Genetic variability of mu-opioid receptor in an obstetric population. Anesthesiology (2004) 100 1030-1033.