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

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 post-operative 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 less than 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.