Pharmacokinetics of M6G following intravenous and oral administration in healthy volunteers

Acute Pain

Volumn 8, Issue 2, 2006, Pages 63-71

  Villesen, Hanne H ^a   Hedal, Birte ^b   Engbaek, Jens ^c   Frokjaer, Sven ^a   Hansen, Steen H ^a   Jensen, Niels Henrik ^c   Rasmussen, Mette ^a   Skram, Ulrik ^d   Stevner, Lene ^a   Christrup, Lona L ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b ROSKILDE HOSPITAL   (Denmark)

^c GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^d Mental Health Center Glostrup   (Denmark)

Author keywords

Absorption; Absorption enhancers; Bioavailability; M6G; Morphine 6 glucuronide; Oral and i.v. administration; Pharmacokinetic

Indexed keywords

MORPHINE 6 GLUCURONIDE; PARACETAMOL; POLYSORBATE 20; SALAZOSULFAPYRIDINE;

ADULT; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CLINICAL TRIAL; COLON; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DUODENUM; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; VOLUNTEER;

EID: 33745671110     PISSN: 13660071     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.acpain.2006.04.001     Document Type: Article

References (27)

1. Romberg R., Olofsen E., Sarton E., den Harting J., Taschner P.E.M., and Dahan A. Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers. Anesthesiology 100 (2004) 120-133
2. Thomson P.I., Joel S., John L., Wedzicha J.A., Maclean M., and Slevin M. Respiratory depression following morphine and morphine-6-glucuronide in normal subjects. Br J Clin Pharmacol 40 (1995) 145-152
3. Skarke C., Darimont J., Schmidt H., Geisslinger G., and Lötsch J. Analgesic effects of morphine and morphine-6-glucuronide in an transcutaneous electric pain model in healthy volunteers. Clin Pharmacol Ther 119 (2003)
4. Cann C., Curran J., Milner T., and Ho B. Unwanted effects of morphine-6-glucoronide and morphine. Anaesthesia 57 (2002) 1200-1203
5. Romberg R., Olofsen E., Sarton E., Teppema L., and Dahan A. Pharmacodynamic effect of morphine-6-glucuronide versus morphine on hypoxic and hypercapnic breathing in healthy volunteers. Anesthesiology 99 (2003) 788-798
6. Peat S.J., Hanna M.H., Woodham M., Knibb A., and Ponte J. Morphine-6-glucuronide: effects on ventilation in normal volunteers. Pain 45 (1991) 101-104
7. Frances B., Gout R., Monsarrat B., Cros J., and Zajac J.-M. Further evidence that morphine-6b-glucuronide is a more potent opioid agonist than morphine. J Pharmacol Exp Ther 262 (1992) 25-31
8. Hanna M.H., Peat S.J., Woodham M., Knibb A., and Fung C. Analgesic efficacy and CSF pharmacokinetics of intrathecal morphine-6-glucuronide: comparison with morphine. Br J Anaesth 64 (1990) 547-550
9. Hanna M.H., Pest S.J., Knibb A.A., and Fung C. Disposition of morphine-6-glucuronideand morphine in healthy volunteers. Br J Anaesth 66 (1991) 103-107
10. Osborne R., Thompson P., Joel S., Trew D., Patel S.S., and Levin M. The analgesic activity of morphine-6-glucuronide. Br J Pharmacol 34 (1992) 130-138
11. Penson R.T., Joel S.P., Roberts M., Gloyne A., Beckwith S., and Slevin M.L. The bioavailability and pharmacokinetics of subcutaneous, nebulized and oral morphine-6-glucuronide. Br J Clin Pharmacol 53 (2002) 347-354
12. Avdeef A. Octanol-, chloroform-, and propylene glycol dipelargonat-water partitioning of morphine-6-glucuronide and other related opiates. J Med Chem 39 (1996) 4377-4381
13. Stain-Texier F., Sandouk P., and Scherrmann J.-M. Intestinal absorption and stability of morphine-6-glucuronide in different physiological compartments of the rat. Drug Metab Dispos 26 (1998) 383-387
14. Chapman DJ. Analysis and pharmacokinetics of morphine and morphine-6-glucuronide. Thesis/Dissertation, UK: University of Surrey; 1990.
15. Lötsch J., Stockmann A., Kobal G., Brune K., Waibel R., Schmidt N., et al. Pharmacokinetics of morphine and its glucuronides after intravenous infusion of morphine and morphine-6-glucuronide in healthy volunteers. Clin Pharmacol Ther 60 (1996) 316-325
16. Lötsch J., Weiss M., Kobal G., and Geisslinger G. Pharmacokinetics of morphine-6-glucuronide and its formation from morphine after intravenous administration. Clin Pharmacol Ther 63 (1998) 629-639
17. Milne R.W., Nation R.L., and 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 28 (1996) 345-472
18. Illum L., Davis S.S., Pawula M., Fisher A.N., Barrett D.A., Farraj N.F., et al. Nasal administration of morphine-6-glucuronide in sheep - a pharmacokinetic study. Biopharm Drug Dispos 17 (1996) 717-724
19. Christrup LL, Frokjaer S, Villesen HH. Morphine-6-glucuronide: the clinical potential after oral administration. Permation of isolated rat gut segments (submitted for publication).
20. Sunesen V.H., Vedelsdal R., Kristensen H.G., Christrup L.L., and Mullertz A. Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug. Eur J Pharm Sci 24 (2005) 297-303
21. Krantz Jr. J.C. Limiting factors in the use of antibiotics. Bull Sci Med (Maryland) 36 (1951) 182-183
22. Steigmann F. Am J Dig Dis 20 (1953) 380
23. Waldstein S.S. Am J Dig Dis 21 (1954) 181
24. Huwyler J., Drewe J., Klusemann C., and Fricker F. Evidence for P-glycoprotein-modulated penetration of morphine-6-glucuronide into brain capillary endothelium. Br J Pharmacol 118 (1996) 1879-1885
25. Bourasset F., Cisternino S., Temsamani J., and Scherrmann J.-M. Evidence for an active transport of morphine-6-glucuronide but not P-glycoprotein-mediated at the blood-brain barrier. J Neurochem 86 (2003) 1564-1567
26. Lötsch J., Schmidt R., Vetter G., Schmidt H., Niederberger E., Geisslinger G., et al. Increased CNS uptake and enhanced antinociception of morphine-6-glucuronide in rats after inhibition of P-glycoprotein. J Neurochem 83 (2002) 241-248
27. Van Crugten J.T., Sallustio B.C., Nation R.L., and Somogyi A.A. Renal tubular transport of morphine, morphine-6-glucuronide, and morphine-3-glucuronide in the isolated perfused rat kidney. Drug Metab Dispos 19 (1991) 1087-1092