Long term methadone for chronic pain: A pilot study of pharmacokinetic aspects

  1. Olav Magnus S. Fredheim1,3,*,
  2. Petter C. Borchgrevink1,4,
  3. Pål Klepstad1,4,
  4. Stein Kaasa2,5,
  5. Ola Dale1,4

Article first published online: 9 JAN 2012

DOI: 10.1016/j.ejpain.2006.09.006

Issue

European Journal of Pain

European Journal of Pain

Volume 11, Issue 6, pages 599–604, August 2007

Additional Information

How to Cite

Fredheim, O. M. S., Borchgrevink, P. C., Klepstad, P., Kaasa, S. and Dale, O. (2007), Long term methadone for chronic pain: A pilot study of pharmacokinetic aspects. European Journal of Pain, 11: 599–604. doi: 10.1016/j.ejpain.2006.09.006

Author Information

  1. 1

    Pain and Palliation Research Group, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, 7006 Trondheim, Norway

  2. 2

    Pain and Palliation Research Group, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

  3. 3

    Department of Medicine, Sandnessjøen Hospital, Helgelandssykehuset, Norway

  4. 4

    Department of Anaesthesia, St. Olav University Hospital, Trondheim, Norway

  5. 5

    Palliative Medicine Unit, Department of Oncology, St. Olav University Hospital, Trondheim, Norway

* Pain and Palliation Research Group, Multidisciplinary pain centre, St. Olav University Hospital, Olav Kyrresgt. 17, 7006 Trondheim, Norway. Tel.: +47 41628318; fax: +47 73866990. olavmagn@frisurf.no

Publication History

  1. Issue published online: 9 JAN 2012
  2. Article first published online: 9 JAN 2012
  3. Received 13 March, 2006; Revised 27 September, 2006; Accepted 27 September, 2006

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Keywords:

  • Methadone;
  • Morphine;
  • Pharmacokinetic;
  • Chronic pain;
  • Opioid switch

Abstract

Methadone is used as an alternative opioid when first line opioids fail to provide adequate pain control. Highly variable morphine:methadone dose ratios make switching challenging and little is known about the pharmacokinetics of long lasting methadone treatment for pain. Twelve patients treated with morphine for chronic non-malignant pain were switched to methadone. Seven of these patients continued with methadone throughout the nine months study period and only minor dose adjustments were performed. Serum concentrations of morphine, methadone and their metabolites were measured at baseline, day one and two, after dose titration and one week, five weeks, three months and nine months after the end of dose titration. Serum concentrations of methadone and its metabolite EDDP did not change significantly from the end of dose titration and during the nine months (repeated measures ANOVA: p = 0.88 and p = 0.06). Very low correlation between dose ratios and serum concentration ratios between morphine and methadone was observed. Large interindividual differences in serum concentrations and metabolism were observed. Our findings contradict that autoinduction of methadone metabolism takes place during long term treatment and supports that a 3-day opioid switch from morphine to methadone followed by a one week titration seems pharmacologically sound.

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