title: Comparative pharmacodynamics and pharmacokinetics of methadone and slow-release oral morphine for maintenance treatment of opioid dependence.
abstract: BACKGROUND
  Slow-release oral morphine (SROM) has been proposed as an alternative maintenance pharmacotherapy to methadone for treatment of opioid dependence. However, the pharmacodynamics and pharmacokinetics of SROM have not been previously assessed in a methadone maintenance population.
  
  
  METHODS
  In 14 methadone maintenance patients reporting adequate (holders, n=7) or inadequate (non-holders, n=7) withdrawal suppression between doses, plasma drug concentrations and indices of opioid effect (withdrawal severity, pupil diameter, and respiratory rate) were determined across a 24 h inter-dosing interval on one occasion at steady-state for methadone and SROM (once-daily Kapanol) using an open-label, crossover design.
  
  
  RESULTS
  Opioid effects were of a similar overall magnitude following dosing for each drug and showed an inverse association with plasma drug concentrations, which peaked later for morphine compared to (R)-methadone (6.5 +/- 2.3 h vs. 2.5 +/- 1.4 h, P<0.001). For methadone non-holders, the number of self-reported opioid withdrawal symptoms prior to dosing was less for SROM compared to methadone (3.4 +/- 2.6 vs. 9.0 +/- 3.2, P<0.01); for holders it was approximately equal (4.4 +/- 3.0 vs. 4.0 +/- 3.7, P<0.76). Maintenance doses were more strongly related to plasma drug concentrations for SROM compared to methadone and may thus be more predictive of therapeutic response for the former medication. Twelve of the 14 subjects preferred SROM to methadone (P=0.01).
  
  
  CONCLUSIONS
  The pharmacodynamics and pharmacokinetics of SROM support its use as an alternative once-daily agonist option in the treatment of opioid dependence, particularly for patients responding poorly to methadone maintenance treatment.
authors.affiliation: Department of Clinical and Experimental Pharmacology, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Mitchell
authors.forename: Jason M
authors.initials: JM
authors.lastname: White
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Somogyi
authors.forename: Felix
authors.initials: F
authors.lastname: Bochner
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008875:Middle Aged; D009020:Morphine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000534:rehabilitation*
chemical_list: D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009020:Morphine; D008691:Methadone