Morphine analgesia in cancer pain: role of the glucuronides.
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.
Penson
Richard T
RT
Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Joel
Simon P
SP
Gloyne
Anna
A
Clark
Simon
S
Slevin
Maurice L
ML
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
D000701:Analgesics, Opioid; D020719:Glucuronides; D009020:Morphine