The unique pharmacokinetics and pharmacodynamics of methadone make it a valuable option in the management of chronic pain. Saliva is a useful tool for monitoring this drug and studying a possible recirculation process. The objective of this study was to identify the recirculation process of methadone in patients with chronic pain using saliva as biological fluid. The concentration-time profiles of methadone in saliva in eight patients with chronic pain were obtained. Morning methadone dose was administered at 8:00 a.m. with 250 mL of water. Times of food ingestion were 4 hours (lunch) and 8 hours (tea) post-dose. Saliva samples were collected using Salivette® devices. Drug quantification in saliva was performed using a validated high performance liquid chromatography method. Immediately after sampling, the pH was measured using a portable pH meter with a semi-micro electrode. Two secondary peaks were observed at 6 and 10 hours post-dose (two hours after food intakes) in the mean concentration-time curve of methadone in saliva. No correlation between saliva pHs and salivary methadone concentrations was observed. Methadone was found to be subject to recirculation, probably via gastric secretion and intestinal reabsorption. Saliva proved to be a more useful tool than plasma to magnify this phenomenon.
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