title: Morphine analgesia in cancer pain: role of the glucuronides.
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). Ml3G: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.
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
authors.forename: Simon P
authors.initials: SP
authors.lastname: Joel
authors.forename: Anna
authors.initials: A
authors.lastname: Gloyne
authors.forename: Simon
authors.initials: S
authors.lastname: Clark
authors.forename: Maurice L
authors.initials: ML
authors.lastname: Slevin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000698:Analgesia / Q000379:methods*; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D020719:Glucuronides / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement
chemical_list: D000701:Analgesics, Opioid; D020719:Glucuronides; D009020:Morphine