Pharmaceutisch Weekblad

, Volume 6, Issue 6, pp 237–240 | Cite as

Preliminary study on the absorption profile after rectal and oral administration of methadone in human volunteers

  • F. Moolenaar
  • G. Fiets
  • J. Visser
  • D. K. F. Meijer
Short Communications


Methadone is a potent, long acting narcotic analgesic which can be orally administered due to its almost complete bioavailability. There is a growing interest in the rectal route of administration in the case of acute postoperative or chronic malignant pain. Since virtually no data were available on the rectal absorption profile of methadone in man, plasma concentrations of methadone were determined by means of HPLC analysis after a single dose of 10 mg methadone HCl in a cross-over pilot study in five volunteers. The rectal dosage forms included aqueous solutions and fatty suppositories. A comparison was made with an orally administered solution. Compared with oral dosing, the extent of rectal absorption from an aqueous solution was almost 80% up to 8 h after dosing. Although the mean peak concentration and the AUC0-8h was significantly lower (p < 0.01), no marked difference in tmax was observed: 2.8 and 3.1 h respectively. Rectal absorption conditions of methadone from fatty suppositories (3 ml) were found to be less favourable. The peak plasma concentration was only reached 3–4 h after administration, whereas the relative bioavailability up to 8 h after dosing ranged from 35–58%. This rate-limiting absorption pattern may be due to the critical solubility properties of methadone HCl at physiological pH.


Plasma Concentration Absorption Profile Dosage Form Peak Plasma Concentration Human Volunteer 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and Pharmacokinetics of methadone during the perioperative period. Anaesthesiology 1982;557:458–67.Google Scholar
  2. 2.
    Nilsson MI, Meresaar U, Anggard E. Clinical Pharmacokinetics of methadone. Acta Anaesthesiol Scand 1982;74:66–9.Google Scholar
  3. 3.
    Breivik H, Rennemo F. Clinical evaluation of combined treatment with methadone and psychotropic drugs in cancer patients. Acta Anaesthesiol Scand 1982;74:135–40.Google Scholar
  4. 4.
    Paalzow L, Nilsson MI, Stenberg P. Pharmacokinetic basis for optimal methadone treatment of pain in cancer patients. Acta Anaesthesiol Scand 1982;74:55–8.Google Scholar
  5. 5.
    Inturrisi CE, Verebely K. Disposition of methadone in man after a single oral dose. Clin Pharmacol Ther 1972;13:923–30.PubMedGoogle Scholar
  6. 6.
    Hanssen J, Ginman P, Hartvig P, et al. Clinical evaluation of oral methadone in treatment of cancer pain. Acta Anaesthesiol Scand 1982:74:124–7.Google Scholar
  7. 7.
    Lindahl S, Olsson AK, Thomson D. Rectal premedication in children. Anaesthesia 1981;36:376–9.PubMedGoogle Scholar
  8. 8.
    Westerling D, Lindahl S, Andersson KE, Andersson A. Absorption and bioavailability of rectally administered morphine in women. Eur J Clin Pharmacol 1982;23:59–64.CrossRefPubMedGoogle Scholar
  9. 9.
    Pannuti F, Rossi AP, Iafelice G, et al. Control of chronic pain in very advanced cancer patients with morphine hydrochloride administered by oral, rectal and sublingual route. Clinical report and preliminary results on morphine pharmacokinetics. Pharmacol Res Comm 1982;14:369–80.Google Scholar
  10. 10.
    Hanning CD, Smith G, McNeill M, Graham NB. Rectal administration of morphine from a sustained release hydrogel suppository. Br J Anaesth 1983;55:236–7.Google Scholar
  11. 11.
    Schulkes JA, Hovinga G. Pijnbestrijding bij patiËnten met kanker. Geneesmiddelenbulletin 1981;15:63–8.Google Scholar
  12. 12.
    Visser J, Grasmeijer G, Moolenaar F. Determination of therapeutic concentrations of codeine by high-performance liquid chromatography. J Chromatogr 1983;274:372–5.PubMedGoogle Scholar
  13. 13.
    Berkowitz BA. The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. Clin Pharmacokinet 1976;1:219–30.PubMedGoogle Scholar
  14. 14.
    Olsen GD, Wendel HA, Livermore JD, Leger RM, Lynn RK, Gerber N. Clinical effects and pharmacokinetics of racemic methadone and its optical isomers. Clin Pharmacol Ther 1977;21:147–57.PubMedGoogle Scholar
  15. 15.
    Olsen GD, Wilson JE, Robertson GE. Respiratory and ventilatory effects of methadone in healthy women. Clin Pharmacol Ther 1981;29:373–80.PubMedGoogle Scholar
  16. 16.
    Moolenaar F, Grasmeijer G, Visser J, Meijer DKF. Rectal versus oral absorption of codeine phosphate in man. Biopharm Drug Dispos 1982;4:195–9.Google Scholar
  17. 17.
    Moolenaar F, Yska JP, Visser J, Meijer DKF. Drastic improvement of the rectal absorption conditions of morphine man. Eur J Clin Pharmacol. submitted for publication.Google Scholar
  18. 18.
    Verebely K, Volavka J, Mulé S, Resnick R. Methadone in man: Pharmacokinetic and excretion studies in acute and chronic treatment. Clin Pharmacol Ther 1975;18:180–90.PubMedGoogle Scholar
  19. 19.
    Schoonen AJM, Moolenaar F, Haverschmidt C, Huizinga T. The interphase transport from fatty suppository bases. Pharm Weekbl 1976;111:585–90.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1984

Authors and Affiliations

  • F. Moolenaar
    • 1
  • G. Fiets
    • 1
  • J. Visser
    • 1
  • D. K. F. Meijer
    • 1
  1. 1.Department of Pharmacology and Pharmacotherapeutics, Subfaculty of PharmacyState University of GroningenAW GroningenThe Netherlands

Personalised recommendations