title: Tolerability and efficacy of two synergistic ratios of oral morphine and oxycodone combinations versus morphine in patients with chronic noncancer pain.
abstract: OBJECTIVE
  Analgesic synergy and improved tolerability have been reported for flexible dose morphine and oxycodone combinations. This report describes two studies with similar double-blind, randomized, 7-day crossover designs (up to 7 days per arm) conducted to 1) explore the analgesic and safety benefit offixed ratio of morphine (M) and oxycodone (0) combinations (MOX) and 2) define the optimal ratio for morphine and oxycodone combination.
  
  
  METHODS
  Clinical study centers in Australia.
  
  
  METHODS
  Patients with chronic noncancer pain.
  
  
  METHODS
  Eligible patients were randomly assigned to receive flexible doses of either M or fixed ratio of MOX (M3:02 in study A; M1:02 in study B). The starting doses of M or MOX were the morphine equivalent doses (MEDs) converted from the analgesics received before entering double-blind treatment. At each crossover period, the doses were titrated to achieve analgesia at steady state, which was defined as when the same total daily dose (+/-10 percent) had been given consecutively for 3 days.
  
  
  METHODS
  The primary endpoint was the study medication dose (MED), which produced adequate pain control at steady state.
  
  
  RESULTS
  Analgesic synergy in MOX was observed in both studies. On an MED basis, 61.6 percent (study A, M:0 = 3:2) or 46.8 percent (study B, M:0 = 1:2) more MED were needed forM monotherapy to achieve steady-state pain control when compared with MOX. Patient tolerability profiles were also generally better in the MOX groups.
  
  
  CONCLUSIONS
  A 3:2 or 1:2 fixed ratio combination of morphine and oxycodone (MOX) produced analgesic synergy and a tolerability profile improvement in patients with chronic noncancer pain.
authors.affiliation: Michigan Technology and Research Institute, Ann Arbor, Michigan, USA.
authors.forename: Felix A
authors.initials: FA
authors.lastname: de la Iglesia
authors.forename: Gary W
authors.initials: GW
authors.lastname: Pace
authors.forename: Gary L W G
authors.initials: GL
authors.lastname: Robinson
authors.forename: Nuo-Yu
authors.initials: NY
authors.lastname: Huang
authors.forename: Warren
authors.initials: W
authors.lastname: Stern
authors.forename: Patricia
authors.initials: P
authors.lastname: Richards
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage* / Q000627:therapeutic use*; D001315:Australia; D059350:Chronic Pain / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects* / Q000627:therapeutic use*; D010098:Oxycodone / Q000009:adverse effects* / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000700:Analgesics; D009020:Morphine; D010098:Oxycodone