Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review

Purpose Despite its availability for more than 70 years, many details concerning methadone remain contentious, such as the dosing equivalents for intravenous and enteral administration. A scoping review was performed to evaluate whether existing literature on methadone bioavailability in human subjects support the current recommendation that an equivalent enteral dose is twice the intravenous dose. Methods A librarian-assisted search of the PubMed and EMBASE databases identified all English-language articles with the terms methadone and bioavailability and/or conversion in the title or abstract published from inception though December 2019. A manual search of references was also performed to identify any additional articles. Studies were included in a scoping review if they were published in English and evaluated methadone bioavailability in human subjects. Results Among 65 publications initially identified, 6 studies involving a total of 50 patients were included in the review. Bioavailability (F) data for healthy volunteers and patients with opioid use disorder, metastatic cancer, chronic pain from malignant or nonmalignant disease were available for analysis. The pooled mean (95% confidence interval) F was 85.4% (75.2%-95.6%), with heterogeneity (I 2) of 0. In the 4 studies that provided individual patient–level data, F was >50% in 40 of 42 patient measurements (95.2%) and ≥75% in 33 of 42 patient measurements (78.6%). Conclusion Available evidence suggests the bioavailability of methadone is generally more than 75%, there is limited evidence for the currently recommended 1:2 ratio (intravenous:enteral), and a more appropriate dosing ratio may be 1:1.3. This scoping review underscores the need for further research to establish an effective and safe ratio when converting between intravenous and enteral dosing formulations of methadone.