Morphine analgesia in cancer pain: Role of the glucuronides

Richard T. Penson, MRCP, MD; Simon P. Joel, PhD; Anna Gloyne, BSc; Simon Clark, BSc; Maurice L. Slevin, FRCP, MD

doi:10.5055/jom.2005.0021

Authors

Richard T. Penson, MRCP, MD
Simon P. Joel, PhD
Anna Gloyne, BSc
Simon Clark, BSc
Maurice L. Slevin, FRCP, MD

DOI:

https://doi.org/10.5055/jom.2005.0021

Keywords:

morphine, cancer pain, glucuronides, analgesia

Abstract

Preclinical data and limited studies in humans have suggested that morphine-6-glucuronide (M6G) has analgesic activity and morphine-3-glucuronide (M3G), contributes adversely to the therapeutic effect of morphine. This open point-prevalence study in 103 patients on oral morphine for cancer-related pain investigated the correlations between morphine doses, metabolites, and the degree of pain relief or toxicity. Morphine, M6G, and M3G were assayed by high-performance liquid chromatography on a single blood sample taken between two and four hours after dose. Pain, analgesia, and toxicity were recorded on numerical and visual analog scales. Patients received a median dose of 60 (range, 10 to 620) mg per day morphine, for a median of 4.1 weeks (range, 0.2 to 46.0 weeks). M3G:M6G ratios fell within a narrow range, with a median value of 4.39 (interquartile range, 3.78 to 6.96; range, 2.18 to 14.95). There were no significant correlations between M3G:M6G and morphine dose, or any measure of analgesia. The correlation between plasma concentration and pain score (i.e., better analgesia) was stronger for M6G (r = 0.308, p < 0.01) than morphine (r = 0.197, p = 0.05). These data suggest that M6G contributes significantly to the analgesic potency of oral morphine. No evidence was found for differences in M3G:M6G ratios contributing to analgesia or toxicity.

Author Biographies

Richard T. Penson, MRCP, MD

Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.

Simon P. Joel, PhD

Department of Medical Oncology, St. Bartholomew’s Hospital, West Smithfield, London, England.

Anna Gloyne, BSc

Department of Medical Oncology, St. Bartholomew’s Hospital, West Smithfield, London, England.

Simon Clark, BSc

Department of Medical Oncology, St. Bartholomew’s Hospital, West Smithfield, London, England.

Maurice L. Slevin, FRCP, MD

Department of Medical Oncology, St. Bartholomew’s Hospital, West Smithfield, London, England.

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