Bioavailabilities of rectal and oral methadone in healthy subjects

Authors

  • Ola Dale,

    Corresponding author
    1. Department of Anaesthesiology, University of Washington, Seattle, Washington, USA
    2. Department of Circulation and Medical Imaging, Norwegian University of Science and Technology and Department of Anaesthesia and Acute Medicine, St. Olavs. University Hospital, Trondheim, Norway
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  • Pamela Sheffels,

    1. Department of Anaesthesiology, University of Washington, Seattle, Washington, USA
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  • Evan D. Kharasch

    1. Department of Anaesthesiology, University of Washington, Seattle, Washington, USA
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Ola Dale, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7489 Trondheim, Norway. Tel: +47 73598849 Fax: +47 73869495 E-mail: ola.dale@medisin.ntnu.no

Abstract

Aims

Rectal administration of methadone may be an alternative to intravenous and oral dosing in cancer pain, but the bioavailability of the rectal route is not known. The aim of this study was to compare the absolute rectal bioavailability of methadone with its oral bioavailability in healthy humans.

Methods

Seven healthy subjects (six males, one female, aged 20–39 years) received 10 mg d5-methadone-HCl rectally (5 ml in 20% glycofurol) together with either d0-methadone intravenously (5 mg) or orally (10 mg) on two separate occasions. Blood samples for the LC-MS analyses of methadone and it's metabolite EDDP were drawn for up to 96 h. Noninvasive infrared pupillometry was peformed at the same time as blood sampling.

Results

The mean absolute rectal bioavalability of methadone was 0.76 (0.7, 0.81), compared to 0.86 (0.75, 0.97) for oral administration (mean (95% CI)). Rectal absorption of methadone was more rapid than after oral dosing with Tmax values of 1.4 (0.9, 1.8) vs. 2.8 (1.6, 4.0) h. The extent of formation of the metabolite EDDP did not differ between routes of administration. Single doses of methadone had a duration of action of at least 10 h and were well tolerated.

Conclusions

Rectal administration of methadone results in rapid absorption, a high bioavailability and long duration of action. No evidence of presystemic elimination was seen. Rectal methadone has characteristics that make it a potential alternative to intravenous and oral administration, particularly in cancer pain and palliative care.

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