The metabolite morphine‐6‐glucuronide contributes to the analgesia produced by morphine infusion in patients with pain and normal renal function Journal Article

  

Authors:	Portenoy, R. K.; Thaler, H. T.; Inturrisi, C. E.; Friedlander‐Klar, H.; Foley, K. M.
Article Title:	The metabolite morphine‐6‐glucuronide contributes to the analgesia produced by morphine infusion in patients with pain and normal renal function
Abstract:	Morphine‐6‐glucuronide is a metabolite of morphine that binds to the opioid receptor and is analgesic in animals and humans. Although accumulation of morphine‐6‐glucuronide in patients with renal insufficiency has been implicated in morphine toxicity, the contribution of the metabolite to morphine analgesia in patients with normal renal function has not been established. To evaluate this contribution, we repeatedly sampled blood and assessed effects during and after a loading infusion with morphine (mean duration, 168 minutes) in 14 patients with chronic pain, all of whom had normal serum creatinine levels. Plasma concentrations of morphine and morphine‐6‐glucuronide were assayed by use of high performance liquid chromatography with electrochemical detection. Patients were divided into three groups on the basis of the molar concentration ratio of morphine‐6‐glucuronide:morphine from the start of the infusion until 240 minutes later: Group 1 (n = 5) had a mean ratio ≥0.7:1; group 2 (n = 4) had a mean ratio ≤0.7:1 but ≥0.4:1; and group 3 (n = 5) had a mean ratio <0.4:1. Time‐effect plots revealed that average and peak relief were greater in group 1 than group 2 and greater in group 2 than group 3. For all patients, mean morphine‐6‐glucuronide:morphine ratio throughout the study was significantly correlated with mean pain relief (r = 0.611, p < 0.02). These data suggest that morphine‐6‐glucuronide contributes to morphine analgesia in patients with normal renal function. The role of the metabolite should be considered when morphine is used clinically. Clinical Pharmacology and Therapeutics (1992) 51, 422–431; doi: © 1992 American Society for Clinical Pharmacology and Therapeutics
Keywords:	adult; clinical article; aged; drug potentiation; pain; creatinine; kidney; kidney function; chronic pain; drug blood level; chromatography, high pressure liquid; morphine; pain measurement; drug metabolite; analgesia; infusions, intravenous; intravenous drug administration; morphine 6 glucuronide; middle age; morphine derivatives; human; male; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title:	Clinical Pharmacology & Therapeutics
Volume:	51
Issue:	4
ISSN:	0009-9236
Publisher:	Nature Publishing Group
Date Published:	1992-04-01
Start Page:	422
End Page:	431
Language:	English
DOI:	10.1038/clpt.1992.42
PUBMED:	1563212
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0026538171&doi=10.1038%2fclpt.1992.42&partnerID=40&md5=a54a1acca38888323a30faf9046684d4
Notes:	Article -- Export Date: 30 July 2019 -- Source: Scopus

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