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Miscellaneous Article

Pharmacokinetics of Methadone

(Assistant Professor) (Assistant Professor) (PhD Candidate) (Associate Professor and Vice-Chair) (Assistant Professor) (Assistant Professor) (PhD Candidate) (Associate Professor and Vice-Chair) (Assistant Professor) (Assistant Professor) (PhD Candidate) (Associate Professor and Vice-Chair) (Assistant Professor) (Assistant Professor) (PhD Candidate) (Associate Professor and Vice-Chair) , &
Pages 13-24 | Received 12 May 2005, Accepted 06 Jun 2005, Published online: 17 Aug 2009
 

Abstract

Methadone is a synthetic opioid that is effective for the relief of moderate-to-severe pain and for the treatment of opioid dependence. The pharmacokinetics of methadone differ from those of morphine in that methadone has a higher bioavailability, a much longer half-life, and is hepatically metabolized by cytochrome P450 enzymes. The pharmacokinetics of methadone are variable and an understanding of the factors that impact the onset, magnitude, and duration of analgesia is required to optimize therapy. Drug interactions are common and patients receiving methadone should be monitored closely for toxicity or therapeutic failure. Special populations in whom a change from the usual dosage regimen may be necessary include pediatric patients, patients with renal failure, the elderly, and pregnant women. To achieve an optimal dosage regimen, the clinician must have an understanding of the pharmacokinetics and pharmacodynamics of methadone in addition to the relationship between these variables and their patient' demographic and pathophysiologic characteristics. A MEDLINE search was performed to identify literature published between 1966 and May 2005 relevant to the pharmacokinetics of methadone. These publications were reviewed and the literature summarized regarding unique and clinically important elements of methadone disposition including its absorption profile, distribution, and metabolism/excretion. General dosing guidelines, dosage conversions from other opioids and pharmacokinetic issues in Special populations are discussed.

Additional information

Notes on contributors

Steven E. Kern

Cherokee Layson-Wolf, PharmD, is Assistant Professor at the University of Maryland School of Pharmacy. At the time that this review was conducted, she was a Community Care Pharmacy Practice Resident at Virginia Commonwealth University.

Perry G. Fine, MD, is Professor of Anesthesiology, School of Medicine and Associate Medical Director, Pain Management Center at the University of Utah Health Sciences Center, Salt Lake City; and National Medical Director, VistaCare, based in Scottsdale, AZ. This commentary is based on an article in Dr. Fine's VistaCare Palliative Medicine Monitor.

Jonathan R. Gavrin, MD, is the Internet editor for the Journal. He is Associate Professor of Anesthesiology and Adjunct Associate Professor of Medicine at the University of Washington School of Medicine; Associate Member, Fred Hutchinson Cancer Research Center; and Associate Director for Clinical Anesthesia Services, Harborview Medical Center.

Philip J. Wiffen, is the Regional Pharmaceutical and Prescribing Adviser, Anglia & Oxford Region of the National Health Service Executive, a member of the Oxford Regional Pain Relief Unit and Coordinating Editor of the Cochrane Collaboration Pain Palliative and Supportive Care Collaborative Review Group.

Philip J. Wiffen, BPharm, MRPharmS, MFPHM (Hon) is Regional Pharmaceutical and Prescribing Adviser, Anglia & Oxford Region of the National Health Service Executive, a member of the Pain Relief Unit, Churchill Hospital, and Coordinating Editor, Cochrane Collaboration Pain Palliative and Supportive Care Collaborative Review Group.

Howard A. Heit, practices pain medicine and addiction medicine in Fairfax, Virginia, and is Assistant Clinical Professor of Medicine at Georgetown University, Washington, DC. Dr. Heit was a member of the Liaison Committee on Pain and Addiction.

Philip J. Wiffen, is Regional Pharmaceutical and Prescribing Adviser, Anglia & Oxford Region of the National Health Service, a member of the Pain Relief Unit at Churchill Hospital and Coordinating Editor of the Cochrane Collaboration Pain Palliative and Supportive Care Collaborative Review Group.

Last Acts is a Robert Wood Johnson Foundation funded campaign to improve end-of-life care by a coalition of professional and consumer organizations. This coalition works to improve palliative care, focused on managing pain and making life better for individuals and families facing death. Last Acts envisions a world in which dying people and their loved ones receive excellent care and are honored and supported by their community.

S. R. Ghooi, MBBS, is a Medical Consultant in New Delhi.

Gustavo G. De Simone is Medical Oncologist (with Diploma in Palliative Medicine) and Pallium Latinoamérica Association Medical Director and Chief, Section on Palliative Care, Hospital Bonorino Udaondo, Bonpland 2287 (1425) Ciudad de Buenos Aires, Argentina ( [email protected].

The Reverend John S. Lunn, RN, MDiv, is Palliative Care and Hospice Consultant, Global Ministries for the Disciples of Christ and United Church of Christ, and former President, Board of Directors, Kauai Hospice, Hawaii.

Jan Stjernswärd, MD, PhD, FRCP (Edin), is Former Chief, Cancer and Palliative Care, World Health Organization, Geneva, Switzerland, and International Director of the Oxford University International Centre for Palliative Care and World Health Organization Collaborating Centre for Palliative Care, Churchill Hospital, Oxford, UK. He also serves on the Steering Committee of the Diana Palliative Care Initiative, Diana Princess of Wales Memorial Fund in the UK, as a Consultant to the Open Society Institute in New York, and continues to serve as a World Health Organization advisor.

Barbara L. Kass-Bartelmes, MPH, CHES, and Ronda Hughes, PhD, wrote this report for the Agency for Health Care Research and Quality (AHRQ) of the U.S. Public Health Service.

Robert J. Adams, PharmD, was at the time of this study Primary Care Resident, Pharmacy Service, Carl T. Hayden Veterans Affairs Medical Center, Phoenix, AZ.

Stephen P. Lordon, MD, was at the time of this study, Attending Physician in the Pain Management Center, University Hospitals and Clinics, and Clinical Assistant Professor of Anesthesiology, School of Medicine;

Arthur G. Lipman, PharmD, is Professor of Pharmacotherapy, College of Pharmacy, Adjunct Professor of Anesthesiology, School of Medicine and Director of Clinical Pharmacology, Pain Management Center, University Hospitals and Clinics; University of Utah Health Sciences Center.

Christopher Stock, PharmD, is Clinical Pharmacist, Substance Abuse Treatment Programs Pharmacist at the George E. Wahlen Veterans Affairs Salt Lake City Health Care System, and Clinical Associate Professor, College of Pharmacy, University of Utah

Perry G. Fine, MD, is Professor of Anesthesiology, School of Medicine, and Attending Physician at the Pain Management Center, University of Utah Health Sciences Center, Salt Lake City, UT; and Senior Medical Advisor, VistaCare, based in Scottsdale, AZ.

Phillip J. Wiffen, BPharm, MRPharmS, MFPHM(Hon), is Director of Training for the U.K. Cochrane Center, a member of the Oxford Regional Pain Relief Unit at Churchill Hospital, and Coordinating Editor of the Cochrane Collaboration Pain Palliative and Supportive Care Collaborative Review Group.

William J. Rusho, MS, RPh, is Professor (Clinical) of Pharmacotherapy, University of Utah College of Pharmacy and a former member of the FDA Advisory Committee on Pharmacy Compounding. He was clinical coordinator of sterile product compounding at the University of Utah Hospitals and Clinics for 32 years.

Jonathan R. Garvin, MD, is Director of Symptom Management and Palliative Care, Hospital of the University of Pennsylvania; Clinical Associate Professor of Anesthesia and Adjunct Associate Professor of Medicine, School of Medicine, University of Pennsylvania, Philadelphia.

Philip J. Wiffen, BPharm, MSc, MRPharmS, MFPHM (Hon), is a member of the Oxford Regional Pain Relief Unit, Churchill Hospital, Coordinating Editor, Cochrane Collaboration Pain Palliative and Supportive Care Collaborative Review Group, and Director of Training, U.K. Cochrane Center.

Dr. Fishman has developed this feature based on columns he has developed in collaboration with the American Pain Foundation Pain Monitor and Discovery Health. Dr. Fishman retains copyright for this material and has granted permission to the Journal of Pain & Palliative Care Pharmacotherapy to publish it.

Mark R. Collen is a self-taught artist and the creator of PAIN Exhibit and the on-line pain art exhibit PainExhibit.com. As a result of an injury and failed back surgery in 1995, Mr. Collen was left with neuropathic pain. He started the PAIN Exhibit in 2001 as a response to years of undertreatment that he endured.

Mr. Collen has created art pieces about his pain and concluded that art is far more effective at communicating the pain experience than are words. His desire to help end undertreatment of pain, coupled with his understanding of the power of art to educate were the seminal factors in the birth of the PAIN Exhibit and PainExhibit.com.

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