title: Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics.
abstract: The aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12-24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours. The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine.
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Paul
authors.initials: P
authors.lastname: Glue
authors.affiliation: Southern District Health Board, Dunedin, New Zealand.
authors.forename: Gavin
authors.initials: G
authors.lastname: Cape
authors.affiliation: Southern District Health Board, Dunedin, New Zealand.
authors.forename: Donna
authors.initials: D
authors.lastname: Tunnicliff
authors.affiliation: University of Auckland, Auckland, New Zealand.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lockhart
authors.affiliation: Zenith Technology, Dunedin, New Zealand.
authors.forename: Fred
authors.initials: F
authors.lastname: Lam
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gray
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Noelyn
authors.initials: N
authors.lastname: Hung
authors.affiliation: Zenith Technology, Dunedin, New Zealand.
authors.forename: C Tak
authors.initials: CT
authors.lastname: Hung
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Sarah
authors.initials: S
authors.lastname: Harland
authors.affiliation: DemeRx, Fort Lauderdale, FL, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Devane
authors.affiliation: DemeRx, Fort Lauderdale, FL, USA.
authors.forename: John
authors.initials: J
authors.lastname: Howes
authors.affiliation: DemeRx, Fort Lauderdale, FL, USA.
authors.forename: Holger
authors.initials: H
authors.lastname: Weis
authors.affiliation: Pharmaceutical Special Projects Group, New York City, NY, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Friedhoff
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004311:Double-Blind Method; D057915:Drug Substitution / Q000379:methods*; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007050:Ibogaine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D009325:Nausea / Q000139:chemically induced; D058850:Opiate Substitution Treatment / Q000009:adverse effects / Q000379:methods*; D009293:Opioid-Related Disorders / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D007050:Ibogaine; D009020:Morphine; C094385:noribogaine; D008691:Methadone
keywords: methadone; morphine; opioid substitution therapy; pharmacodynamics; pharmacokinetics; safety