{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:17:46Z","timestamp":1792808266446,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 65 publications initially identified, 6 studies involving a total of 50 patients were included in the review. Bioavailability 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) bioavailability (F) was 85.4% (75.2%-95.6%), with heterogeneity (I2) of 0. In the 4 studies that provided individual patient\u2013level data, F was &amp;gt;50% in 40 of 42 patient measurements (95.2%) and \u226575% in 33 of 42 patient measurements (78.6%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajhp\/zxab166","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T04:53:26Z","timestamp":1618894406000},"source":"Crossref","is-referenced-by-count":7,"title":["Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review"],"prefix":"10.1093","author":[{"given":"JiTong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Critical Care, Maine Medical Center, Portland, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Critical Care, Maine Medical Center, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R","family":"Riker","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care, Department of Medicine, Maine Medical Center, Portland, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy Y","family":"Craig","sequence":"additional","affiliation":[{"name":"Maine Medical Center Research Institute, Scarborough, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina J","family":"McKelvy","sequence":"additional","affiliation":[{"name":"Department of Library Services, Portland, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather D","family":"Kemp","sequence":"additional","affiliation":[{"name":"Department of Library Services, Portland, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie D","family":"Nichols","sequence":"additional","affiliation":[{"name":"University of New England College of Pharmacy, Portland, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles L","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Critical Care, Maine Medical Center, Portland, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"issue":"2","key":"2021070810221641000_CIT0001","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/02791072.1991.10472226","article-title":"A brief history of methadone in the treatment of opioid dependence: a personal perspective","volume":"23","author":"Payte","year":"1991","journal-title":"J Psychoactive Drugs"},{"key":"2021070810221641000_CIT0002","article-title":"Executive summary","volume-title":"Federal Regulation of Methadone Treatment","author":"Institute of Medicine Committee on Federal Regulation of Methadone Treatment","year":"1995"},{"issue":"14","key":"2021070810221641000_CIT0003","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2165\/00003088-200241140-00003","article-title":"Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence","volume":"41","author":"Eap","year":"2002","journal-title":"Clin Pharmacokinet"},{"key":"2021070810221641000_CIT0004","first-page":"1936","article-title":"Effective medical treatment of opiate addiction. National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction","volume":"280","year":"1998","journal-title":"JAMA"},{"issue":"2","key":"2021070810221641000_CIT0005","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/cc11250","article-title":"Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial","volume":"16","author":"Wanzuita","year":"2012","journal-title":"Crit Care"},{"issue":"9","key":"2021070810221641000_CIT0006","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1345\/aph.1R132","article-title":"Impact of enteral methadone on the ability to wean off continuously infused opioids in critically ill, mechanically ventilated adults: a case-control study","volume":"46","author":"Al-Qadheeb","year":"2012","journal-title":"Ann Pharmacother"},{"issue":"4","key":"2021070810221641000_CIT0007","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1056\/NEJMra1800222","article-title":"Opioid tolerance in critical illness","volume":"380","author":"Martyn","year":"2019","journal-title":"N Engl J Med."},{"issue":"10","key":"2021070810221641000_CIT0008","doi-asserted-by":"crossref","first-page":"536","DOI":"10.5694\/j.1326-5377.2000.tb139323.x","article-title":"The rediscovery of methadone for cancer pain management","volume":"173","author":"Ayonrinde","year":"2000","journal-title":"Med J Aust"},{"issue":"1","key":"2021070810221641000_CIT0009","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/CCM.0b013e3182783b72","article-title":"Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit","volume":"41","author":"Barr","year":"2013","journal-title":"Crit Care Med"},{"issue":"1","key":"2021070810221641000_CIT0010","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0304-3959(96)03313-1","article-title":"Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: clinical observations","volume":"70","author":"Manfredi","year":"1997","journal-title":"Pain"},{"issue":"10","key":"2021070810221641000_CIT0011","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1200\/JCO.1999.17.10.3307","article-title":"Rapid switching from morphine to methadone in cancer patients with poor response to morphine","volume":"17","author":"Mercadante","year":"1999","journal-title":"J Clin Oncol"},{"issue":"5","key":"2021070810221641000_CIT0012","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1177\/0269216311406577","article-title":"Conversion ratios for opioid switching in the treatment of cancer pain: a systematic review","volume":"25","author":"Mercadante","year":"2011","journal-title":"Palliat Med"},{"key":"2021070810221641000_CIT0013","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jcrc.2016.03.023","article-title":"Methadone analgesia in the critically ill","volume":"34","author":"Elefritz","year":"2016","journal-title":"J Crit Care"},{"key":"2021070810221641000_CIT0014","volume-title":"Package insert","author":"Methadone","year":"2006"},{"issue":"4","key":"2021070810221641000_CIT0015","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.jpain.2014.01.494","article-title":"Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society","volume":"15","author":"Chou","year":"2014","journal-title":"J Pain"},{"issue":"5","key":"2021070810221641000_CIT0016","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/imj.12401","article-title":"Opioid conversion ratios used in palliative care: is there an Australian consensus?","volume":"44","author":"Syrmis","year":"2014","journal-title":"Intern Med J"},{"issue":"7","key":"2021070810221641000_CIT0017","doi-asserted-by":"crossref","first-page":"467","DOI":"10.7326\/M18-0850","article-title":"PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation","volume":"169","author":"Tricco","year":"2018","journal-title":"Ann Intern Med"},{"key":"2021070810221641000_CIT0018","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1756-0500-5-52","article-title":"Meta-analyses and forest plots using a Microsoft Excel spreadsheet: step-by-step guide focusing on descriptive data analysis","volume":"5","author":"Neyeloff","year":"2012","journal-title":"BMC Res Notes."},{"issue":"6","key":"2021070810221641000_CIT0019","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/BF00542102","article-title":"Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method","volume":"20","author":"Meresaar","year":"1981","journal-title":"Eur J Clin Pharmacol"},{"issue":"4","key":"2021070810221641000_CIT0020","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/BF00548404","article-title":"Pharmacokinetics of methadone during maintenance treatment: adaptive changes during the induction phase","volume":"22","author":"Nilsson","year":"1982","journal-title":"Eur J Clin Pharmacol"},{"issue":"3","key":"2021070810221641000_CIT0021","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0304-3959(86)90234-4","article-title":"A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer","volume":"25","author":"Gourlay","year":"1986","journal-title":"Pain"},{"issue":"3","key":"2021070810221641000_CIT0022","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/00007691-199606000-00001","article-title":"Stereoselective pharmacokinetics of methadone in chronic pain patients","volume":"18","author":"Kristensen","year":"1996","journal-title":"Ther Drug Monit"},{"issue":"5","key":"2021070810221641000_CIT0023","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1067\/mcp.2002.128386","article-title":"Disposition of nasal, intravenous, and oral methadone in healthy volunteers","volume":"72","author":"Dale","year":"2002","journal-title":"Clin Pharmacol Ther"},{"issue":"2","key":"2021070810221641000_CIT0024","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1365-2125.2004.02116.x","article-title":"Bioavailabilities of rectal and oral methadone in healthy subjects","volume":"58","author":"Dale","year":"2004","journal-title":"Br J Clin Pharmacol"},{"issue":"3","key":"2021070810221641000_CIT0025","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1080\/15360280802251199","article-title":"Conversion from parenteral to oral methadone","volume":"22","author":"Gonz\u00e1lez-Barboteo","year":"2008","journal-title":"J Pain Palliat Care Pharmacother"},{"issue":"8","key":"2021070810221641000_CIT0026","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.mayocp.2013.05.012","article-title":"A decade of reversal: an analysis of 146 contradicted medical practices","volume":"88","author":"Prasad","year":"2013","journal-title":"Mayo Clin Proc"},{"issue":"3","key":"2021070810221641000_CIT0027","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/cpt196783415","article-title":"A clinical comparison of the analgesic effects of methadone and morphine administered intramuscularly, and of orally and parenterally administered methadone","volume":"8","author":"Beaver","year":"1967","journal-title":"Clin Pharmacol Ther"},{"issue":"2","key":"2021070810221641000_CIT0028","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1056\/NEJM198507113130205","article-title":"The treatment of cancer pain","volume":"313","author":"Foley","year":"1985","journal-title":"N Engl J Med"},{"issue":"3","key":"2021070810221641000_CIT0029","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.jpainsymman.2018.12.001","article-title":"Safe and appropriate use of methadone in hospice and palliative care: expert consensus white paper","volume":"57","author":"McPherson","year":"2019","journal-title":"J Pain Symptom Manage"},{"issue":"2","key":"2021070810221641000_CIT0030","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jpainsymman.2008.04.007","article-title":"Methadone: a closer look at the controversy","volume":"36","author":"Gaertner","year":"2008","journal-title":"J Pain Symptom Manage"},{"key":"2021070810221641000_CIT0031","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0304-3940(97)13391-2","article-title":"The d- and l-isomers of methadone bind to the non-competitive site on the N-methyl-d-aspartate (NMDA) receptor in rat forebrain and spinal cord","volume":"223","author":"Gorman","year":"1997","journal-title":"Neurosci Lett"},{"issue":"4","key":"2021070810221641000_CIT0032","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/j.1360-0443.2011.03374.x","article-title":"(R)-methadone versus racemic methadone: what is best for patient care?","volume":"106","author":"McCance-Katz","year":"2011","journal-title":"Addiction"},{"issue":"3","key":"2021070810221641000_CIT0033","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/ALN.0b013e3181642938","article-title":"Role of CYP2B6 in stereoselective human methadone metabolism","volume":"108","author":"Totah","year":"2008","journal-title":"Anesthesiology"},{"issue":"7","key":"2021070810221641000_CIT0034","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2217\/14622416.8.7.743","article-title":"Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance","volume":"8","author":"Zanger","year":"2007","journal-title":"Pharmacogenomics"},{"issue":"7","key":"2021070810221641000_CIT0035","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1111\/j.1399-6576.2008.01597.x","article-title":"Clinical pharmacology of methadone for pain","volume":"52","author":"Fredheim","year":"2008","journal-title":"Acta Anaesthesiol Scand"},{"issue":"4","key":"2021070810221641000_CIT0036","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/clpt.1987.47","article-title":"Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain","volume":"41","author":"Inturrisi","year":"1987","journal-title":"Clin Pharmacol Ther"},{"key":"2021070810221641000_CIT0037","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12874-016-0116-4","article-title":"A scoping review on the conduct and reporting of scoping reviews","volume":"16","author":"Tricco","year":"2016","journal-title":"BMC Med Res Methodol"}],"container-title":["American Journal of Health-System Pharmacy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ajhp\/advance-article-pdf\/doi\/10.1093\/ajhp\/zxab166\/38385329\/zxab166.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ajhp\/advance-article-pdf\/doi\/10.1093\/ajhp\/zxab166\/38385329\/zxab166.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T18:52:28Z","timestamp":1625770348000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajhp\/advance-article\/doi\/10.1093\/ajhp\/zxab166\/6238008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":37,"URL":"https:\/\/doi.org\/10.1093\/ajhp\/zxab166","relation":{},"ISSN":["1079-2082","1535-2900"],"issn-type":[{"value":"1079-2082","type":"print"},{"value":"1535-2900","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]},"article-number":"zxab166"}}