Cerebrospinal fluid and plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in patients before and after initiation of intracerebroventricular morphine for cancer pain management

Smith, M. T., Wright, A. W., Williams, B., Stuart, G. and Cramond, T. R. (1999) Cerebrospinal fluid and plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in patients before and after initiation of intracerebroventricular morphine for cancer pain management. Anesthesia and analgesia, 88 1: 109-116.

Document type: Journal Article
Collection: Centre for Integrated Preclinical Drug Development Publications

Author(s) Smith, M. T.
Wright, A. W.
Williams, B.
Stuart, G.
Cramond, T. R.
Title Cerebrospinal fluid and plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in patients before and after initiation of intracerebroventricular morphine for cancer pain management
Journal name Anesthesia and analgesia
Publication date 1999
Sub-type Article
Volume number 88
Issue number 1
ISSN 0003-2999
Start page 109
End page 116
Total pages 8
Editor(s) R. D. Miller
Place of publication Baltimore, MD.
Publisher Lippincott Williams & Wilkins
Collection year 1999
Language eng
Subject C1
730104 Nervous system and disorders
320503 Clinical Pharmacology and Therapeutics
Abstract Twenty-three patients treated with intracerebroventricular (ICV) morphine in this study not only obtained excellent pain relief without rapid increases in dose, but also experienced a reduction in morphine-related side effects. By 24 h after initiation of ICV morphine, the mean trough cerebrospinal fluid (CSF) morphine concentration (approximately 20 mu M) was 50-fold higher than the baseline concentration (approximately 0.4 mu M), and the CSF concentration of morphine-6-glucuronide (M6G) was undetectable (<0.01 mu M). The mean CSF concentration of morphine-3-glucuronide (M3G) decreased 90%, from a baseline concentration of 1 mu M to 0.1 mu M by Day 7 postventriculostomy. Thereafter, the mean trough CSF M3G concentration remained relatively constant while ICV morphine was continued, although the concomitant M3G plasma concentrations were undetectable (<0.01 mu M). The large increase in the CSF morphine concentration in patients receiving ICV morphine strongly suggests that increased CSF morphine levels are unlikely to be the primary cause of analgesic tolerance or undesirable excitatory side effects (hyperalgesia, myoclonus, seizures) experienced by some patients receiving chronic large-dose systemic morphine. Implications: After initiation of intracerebroventricular morphine, cancer patients experienced excellent pain relief. Although the mean morphine concentration in cerebrospinal fluid increased 50-fold relative to preventriculostomy levels, rapid dose increases did not occur, which suggests that increased cerebrospinal fluid morphine levels are unlikely to be the main cause of analgesic tolerance.
Keyword(s) Anesthesiology
Intraventricular Morphine
Antinociception
Rat
Metabolites
Disposition
Antagonist
Analgesia
 
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