title: Pain, sedation and morphine metabolism in cancer patients during long-term treatment with sustained-release morphine.
abstract: BACKGROUND
  Morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) are the two most important metabolites of morphine. Both are pharmacologically active, however, with different effects. M-6-G has been demonstrated capable of inducing anti-nociception and sedation, and M-3-G may induce behavioural excitation and possibly antagonise anti-nociception. Their impact on pharmacodynamics in patients in long-term treatment with oral morphine remains to be settled.
  
  
  METHODS
  Forty-two cancer patients treated with oral sustained-release (SR) morphine were assessed for pain, sedation and other side effects related to morphine treatment. Blood samples were analysed for morphine, M-3-G and M-6-G by high-performance liquid chromatography (HPLC).
  
  
  RESULTS
  Significant correlations were found between the daily dose of SR morphine and plasma morphine (M) (r = 0.535, P < 0.001), plasma M-6-G (r = 0.868, P < 0.001) and plasma M-3-G (r = 0.865, P < 0.001). There was no relationship between plasma morphine, M-6-G, M-6-G/M and pain and sedation scores. Seventy-nine percent of the patients suffered from dryness of the mouth, which was the most frequent side effect observed. Patients in this group had higher plasma morphine and M-6-G concentrations than patients who did not suffer from this side effect.
  
  
  CONCLUSIONS
  The plasma concentrations of morphine and its metabolites, M-3-G and M-6-G, are significantly correlated to the daily dose of SR morphine. Although M-6-G has analgesic properties, no associations were found between pain and plasma morphine and morphine metabolites. This may be due to the multitudinous factors affecting the dose-effect relationship. Patients with dryness of the mouth had higher concentrations of morphine and M-6-G than patients without this side effect.
authors.affiliation: Multidisciplinary Pain Centre, Herlev University Hospital, Herlev 2730, Copenhagen, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: Andersen
authors.forename: N H
authors.initials: NH
authors.lastname: Jensen
authors.forename: L
authors.initials: L
authors.lastname: Christrup
authors.forename: S H
authors.initials: SH
authors.lastname: Hansen
authors.forename: P
authors.initials: P
authors.lastname: Sjøgren
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D009022:Morphine Derivatives / Q000097:blood; D009369:Neoplasms / Q000150:complications / Q000378:metabolism; D010146:Pain / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide