title: Impact of anti-cancer drugs and other determinants on serum protein binding of morphine 6-glucuronide.
abstract: OBJECTIVE
  The aim of the present study was to examine factors that may influence the protein binding of morphine 6-glucuronide (M6G), the most active metabolite of morphine.
  
  
  METHODS
  An enzyme-linked immunoabsorbent assay technique was used to measure the M6G concentration in serum of 18 healthy adults, 18 neonatal and 7 children with cancer. Total and free M6G concentrations were measured following equilibrium dialysis for 3 hrs and at physiological pH at 37°C. The influence of vincristine, methotrexate, 6-mercaptopurine, morphine, human albumin, alpha-1-acid glycoprotein, palmitic acid, oleic acid and pH on M6G protein binding was examined.
  
  
  RESULTS
  M6G was 66.87±0.73 percent free in human serum at physiological pH and temperature. The percentage free (unbound) was increased significantly by vincristine (4.33%) and methotrexate (9.68%), but 6- mercaptopurine and morphine had no significant effect on it. Free percentages of M6G was reduced by decreasing serum albumin concentration but was unaffected by the presence of alpa-1-acid glycoprotein (AAG) or changes in serum pH. Similar results were obtained in human serum albumin (HAS) solutions. Addition of palmitic acid and oleic acid reduced protein binding significantly by 6.3% and 7.4%, respectively.
  
  
  CONCLUSIONS
  Although M6G in this study was not highly bounded, but because of its high analgesic potency, any change in its free concentration due to concurrent medication or disease caused significant changes in its effects. This dearth of evidence has been implicated in the reluctance of professionals to be cautious in prescribing them to children, particularly in the neonatal period.
authors.affiliation: National public Health Management research center (NPMC), Department of Clinical Pharmacy.
authors.forename: S O
authors.initials: SO
authors.lastname: Mashayekhi
authors.forename: M
authors.initials: M
authors.lastname: Ghandforoush-Sattari
authors.forename: D C
authors.initials: DC
authors.lastname: Buss
authors.forename: P A
authors.initials: PA
authors.lastname: Routledge
authors.forename: R Dw
authors.initials: RD
authors.lastname: Hain