Pharmacy World & Science

, Volume 32, Issue 6, pp 737–743 | Cite as

Relationship between plasma concentrations of morphine and its metabolites and pain in cancer patients

  • Tomoya SakuradaEmail author
  • Shinya Takada
  • Hisae Eguchi
  • Keishiro Izumi
  • Nobunori Satoh
  • Shiro Ueda
Research Article


Objective This study was undertaken to investigate the relationship between the plasma concentration of morphine, morphine-3-glucuronide and morphine-6-glucuronide and pain in cancer patients receiving oral morphine. Methods The trough value of plasma concentrations of morphine and its metabolites were measured by high performance liquid chromatography using an ultraviolet detector. Using this assay system, the plasma concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide in 26 cancer pain patients were measured and compared with pain intensity. The pain intensity was assessed at the time of blood sampling using the visual analog scale. Results The trough value of morphine and morphine-6-glucuronide did not show a significant correlation with pain intensity by visual analog scale assessment, but morphine-3-glucuronide and the ratio of morphine-3-glucuronide/morphine showed a significantly positive correlation (r = 0.528, P = 0.006 and r = 0.671, P < 0.001, respectively). By dividing the group according to low (≤ median value) or high (> median value) VAS scores a significant difference was found between the two groups in morphine-3-glucuronide and the ratio of morphine-3-glucuronide/morphine (P = 0.045 and P = 0.007, respectively). Conclusion These results indicated that the level of morphine-3-glucuronide is related to the patient’s perception of morphine effect, and the plasma concentration of morphine-3-glucuronide and the ratio of morphine-3-glucuronide/morphine indicated potency to assess clinical effect.


Cancer pain Morphine Morphine-3-glucuronide Morphine-6-glucuronide Pain assessment Plasma concentration 




Conflict of interest

The authors declare no conflict of interest directly relevant to the content of this manuscript.


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Tomoya Sakurada
    • 1
    Email author
  • Shinya Takada
    • 2
  • Hisae Eguchi
    • 3
  • Keishiro Izumi
    • 4
  • Nobunori Satoh
    • 5
  • Shiro Ueda
    • 1
  1. 1.Department of Drug Information and CommunicationGraduate School of Pharmaceutical Sciences, Chiba UniversityChuo-kuJapan
  2. 2.Department of PharmacyNational Hospital Organization Hokkaido Cancer CenterSapporoJapan
  3. 3.Department of PharmacyNational Hospital Organization Shikoku Cancer CenterMatsuyamaJapan
  4. 4.Department of PharmacyNational Cancer Center Hospital EastKashiwaJapan
  5. 5.Department of Clinical Education and ResearchGraduate School of Pharmaceutical Sciences, Chiba UniversityChuo-kuJapan

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