Advertisement

Clinical Drug Investigation

, Volume 18, Issue 2, pp 125–132 | Cite as

Explorative Pharmacokinetic Study of Preoperative Administration of Morphine 50mg Sustained-Release Capsules (Kapanol™ to Surgical Patients

  • Leo H. D. J. Booij
  • Tom B. Vree
  • Heleen Koppers-Hoyset
  • Aart J. Lagerwerf
Clinical Pharmacokinetics

Abstract

Objective: This study investigated the release, absorption and elimination profile of preoperatively administered sustained-release morphine (Kapanol™) and its metabolites in patients undergoing surgery and general anaesthesia.

Methods: Sustained-release morphine 50mg (37.6mg of morphine base) was administered 1 to 2 hours before induction of anaesthesia in 10 patients undergoing elective surgery.

Results: Mean plasma concentration-time curves showed a time to peak concentration (tmax) of 8.4 ± 6.5 hours for morphine and 10.4 ± 10.3 hours for both morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G). The absorption half-life of morphine was 5.7 ± 6.9 hours. The ratio of the areas under the concentration-time curves for morphine, M6G and M3G was 1: 3.5: 28. The elimination half-lives of morphine and its metabolites were not significantly different at 15.0 ± 8.95 hours.

Conclusions: After preoperative oral administration, sustained-release morphine 50mg was absorbed perioperatively in all 10 patients studied. The mean plasma concentration-time curve for morphine resembled that in healthy (nonsurgical) adult males receiving a single dose, and the concentrations attained would be expected to provide postoperative analgesia.

Keywords

Morphine Adis International Limited Mean Residence Time Clin Drug Invest Postoperative Pain Management 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Breivik H. Postoperative pain management: why is it difficult to show that it improves outcome? Eur J Anaesthesiol 1998; 15:748–51PubMedCrossRefGoogle Scholar
  2. 2.
    Breivik H, Högström H, Neimi G. Safe and effective postoperative pain relief: introduction and continuous quality improvement of comprehensive post-operative pain management programmes. Ballière’s Clin Anaesth 1995; 9: 423–60CrossRefGoogle Scholar
  3. 3.
    Roseag OP, Lui AC, Vicutti NJ, et al. Peri-operative multimodal pain therapy for caesarean section: analgesia and fitness for discharge. Can J Anaesth 1997; 44: 803–9CrossRefGoogle Scholar
  4. 4.
    Broomhead A, Kerr R, Tester W, et al. Comparison of a one-a-day sustained release morphine formulation with standard oral morphine treatment for cancer pain. J Pain Symptom Manage 1997; 14: 63–73PubMedCrossRefGoogle Scholar
  5. 5.
    Joshi GP. Postoperative pain management. Int Anesthesiol Clin 1994; 32: 113–26PubMedCrossRefGoogle Scholar
  6. 6.
    Zandsberg S, Rosenblum M. Nonconventional drug administration in anesthesia. Anesth Clin North Am 1994; 12: 17–38Google Scholar
  7. 7.
    Berg-Dahl J. Neuronal plasticity and pre-emptive analgesia: implications for the management of postoperative pain. Dan Med Bull 1994; 41: 434–42Google Scholar
  8. 8.
    Bamber MJ, Tweedie IE, Breeze C, et al. Premedication with controlled release diclofenac sodium reduces post-operative pain after minor gynaecological surgery. Eur J Anaesthesiol 1997; 14: 421–7PubMedCrossRefGoogle Scholar
  9. 9.
    Woolf CJ, Chong MS. Pre-emptive analgesia; treating postoperative pain by preventing the establishment of central sensitisation. Anesth Analg 1993; 77: 329–31Google Scholar
  10. 10.
    Gourlay GK, Plummer JL, Cherry DA, et al. A comparison of Kapanol (a new sustained release morphine formulation), MST Continus, and morphine solution in cancer patients: pharmacokinetic aspects of morphine and morphine metabolites. Proceedings of the 7th World Congress on Pain, 1994; 2:631–43Google Scholar
  11. 11.
    Clinical Investigator Brochure Kapanol™ Capsules. Glaxo Australia Pty Ltd. 3rd ed. March 1993Google Scholar
  12. 12.
    Flöter T, Koch EMW. Comparison of two oral morphine formulations for chronic severe pain of malignant and non-malignant origin: Kapanol vs MST. Clin Drug Invest 1997; 14: 183–91CrossRefGoogle Scholar
  13. 13.
    Wall PD. The prevention of post operative pain. Pain 1988; 33: 289–90PubMedCrossRefGoogle Scholar
  14. 14.
    Koopman-Kimenai PM, Vree TB, Cress-Tijhuis MW, et al. High performance liquid chromatography and preliminary pharmacokinetics of nicomorphine and its metabolites 3-nicotinoyl- and 6-nicotinoylmorphine and morphine. J Chromatogr 1987; 416: 382–7PubMedCrossRefGoogle Scholar
  15. 15.
    Proost JH, Meijer DKW MW/Pharm, an integrated software package for drug dosage regimen calculation and therapeutic drug monitoring. Comp Biol Med 1992; 22: 155–62CrossRefGoogle Scholar
  16. 16.
    Hasselström J, Säwe J. Morphine pharmacokinetics and metabolism in humans. Clin Pharmacokinet 1993; 24: 344–54PubMedCrossRefGoogle Scholar
  17. 17.
    Lötsch J, Stockmann A, Kobal G, et al. Pharmacokinetics of morphine and its glucuronides after intravenous infusion of morphine and morphine-6-glucuronide in healthy volunteers. Clin Pharmacol Ther 1996; 60: 316–25PubMedCrossRefGoogle Scholar
  18. 18.
    Maccarone C, West RJ, Broomhead AF, et al. Single dose pharmacokinetics of Kapanol, a new oral sustained-release morphine formulation. Drug Invest 1994; 7: 262–74Google Scholar
  19. 19.
    Houston JB. Kinetics of disposition of xenobiotics and their metabolites. Drug Metabol Drug Interact 1988; 6: 47–83PubMedGoogle Scholar
  20. 20.
    Bodd E, Jacobsen D, Lund E, et al. Morphine-6-glucuronide might mediate the prolonged opioid effect of morphine in acute renal failure. Hum Exp Toxicol 1990; 9: 317–21PubMedCrossRefGoogle Scholar
  21. 21.
    Milne RW, Nation RL, Somogyi AA. The disposition of morphine and its 3- and 6-glucuronide metabolites in humans and animals, and the importance of the metabolites of the pharmacological effects of morphine. Drug Metab Rev 1996; 28: 345–72PubMedCrossRefGoogle Scholar
  22. 22.
    Hanna MH, Peat SJ, Knibb AA, et al. Disposition of morphine-6-glucuronide and morphine in healthy volunteers. Br J Anaesth 1991; 66: 103–7PubMedCrossRefGoogle Scholar
  23. 23.
    Portenoy RK, Thaler HT, Inturrisi CE, et al. The metabolite morphine-6-glucuronide contributes to the analgesia produced by morphine infusion in patients with pain and normal renal function. Clin Pharmacol Ther 1992; 51: 422–31PubMedCrossRefGoogle Scholar
  24. 24.
    Francés B, Gout R, Campistron G, et al. Morphine-6-glucuronide is more mu-selective and potent in analgesic tests than morphine. The International Narcotics Research Conference (INRC) 1989. New York: AR Liss Inc, 1990: 477–80Google Scholar
  25. 25.
    Thompson PI, Hucks D, McLoughlin L, et al. Comparative opiate receptor affinities of morphine and its active metabolite morphine-6-glucuronide [abstract]. Br J Cancer 1990; 62:484CrossRefGoogle Scholar
  26. 26.
    Hagen NA, Foley KM, Cerbone DJ, et al. Chronic nausea and morphine-6-glucuronide. J Pain Symptom Manage 1991; 6: 125–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • Leo H. D. J. Booij
    • 1
  • Tom B. Vree
    • 1
  • Heleen Koppers-Hoyset
    • 1
  • Aart J. Lagerwerf
    • 1
  1. 1.Institute of AnaesthesiologyAcademic Hospital Nijmegen Sint RadboudGA NijmegenThe Netherlands

Personalised recommendations