title: Plasma morphine and metabolite concentrations are associated with clinical effects of morphine in cancer patients.
abstract: BACKGROUND
  Morphine is the opioid of choice for cancer-related pain, but for many patients the benefits of morphine are outweighed by its side effect profile. Morphine is metabolized to morphine-3-glucuronide and morphine-6-glucuronide; however, little is known about the contribution of these metabolites to analgesia and morphine-related side effects.
  
  
  OBJECTIVE
  We investigated the association between plasma morphine and metabolite concentrations and the clinical effects of morphine in cancer patients.
  
  
  METHODS
  A prospective study was performed in cancer patients taking oral morphine for moderate-to-severe cancer pain. Subjects who responded well to morphine (responders) and subjects who failed to respond to morphine because of lack of analgesia and/or the presence of intolerable side effects (nonresponders/switchers) were recruited. Pain and toxicity scores were recorded and blood samples were analyzed for plasma morphine, morphine-3-glucuronide, and morphine-6-glucuronide concentrations.
  
  
  RESULTS
  Results showed that 1) morphine responders have higher plasma morphine and metabolite concentrations compared with nonresponders, 2) lower pain scores are associated with higher plasma morphine and metabolite concentrations, 3) central side effects are associated with a higher metabolite:plasma morphine ratio, and 4) myoclonus is associated with extremely high concentrations of plasma morphine and metabolites.
  
  
  CONCLUSIONS
  This study has shown that plasma morphine and metabolite concentrations are associated with the clinical effects of morphine therapy. These results are important because they demonstrate the relevance of measuring plasma metabolite concentrations in clinical trials and the potential for metabolite data to deepen our understanding of factors that influence an individual's response to morphine.
authors.affiliation: The Royal Marsden Hospital, London, United Kingdom. sgretton@gmail.com
authors.forename: Sophy K
authors.initials: SK
authors.lastname: Gretton
authors.forename: Joy R
authors.initials: JR
authors.lastname: Ross
authors.forename: Dag
authors.initials: D
authors.lastname: Rutter
authors.forename: Hiroe
authors.initials: H
authors.lastname: Sato
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Droney
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Welsh
authors.forename: Simon
authors.initials: S
authors.lastname: Joel
authors.forename: Julia
authors.initials: J
authors.lastname: Riley
mesh_terms: D000701:Analgesics, Opioid / Q000097:blood / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015984:Causality; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000097:blood* / Q000627:therapeutic use; D009369:Neoplasms / Q000097:blood* / Q000453:epidemiology* / Q000451:nursing; D009293:Opioid-Related Disorders / Q000097:blood* / Q000453:epidemiology*; D010146:Pain / Q000097:blood* / Q000453:epidemiology / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects / Q000706:statistics & numerical data; D015995:Prevalence; D012307:Risk Factors; D013223:Statistics as Topic; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000701:Analgesics, Opioid; D015415:Biomarkers; D009020:Morphine