Document Detail


Morphine in postoperative patients: pharmacokinetics and pharmacodynamics of metabolites.
MedLine Citation:
PMID:  17578959     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: There is great variability in the need for morphine in the postoperative period. We performed a pharmacokinetic-pharmacodynamic study considering the potential effect of the two main metabolites of morphine. METHODS: Fifty patients with moderate to severe pain received morphine as an IV titration, followed by IM administration postoperatively. The plasma concentration of morphine, morphine-6-glucuronide (M-6-G), morphine-3-glucuronide (M-3-G), and pain intensity were measured at frequent intervals. Pharmacokinetic and pharmacodynamic fitting was performed with the software NONMEM. RESULTS: The pharmacokinetics were largely predictable. M-6-G and M-3-G clearances were markedly decreased in patients with renal failure. The pharmacodynamics was less predictable, with an important interindividual variability. M-6-G was 7.8 times more potent than morphine, but the average time to peak concentration in the effect compartment after a bolus injection of morphine was 4.25 h for M-6-G, when compared to 0.33 h for morphine. M-3-G showed mild inhibition of the analgesic properties of morphine and of M-6-G. The time to M-3-G peak concentration in the effect compartment after a bolus injection of morphine was 10 h. CONCLUSIONS: M-6-G is a potent opioid agonist and M-3-G a mild opioid antagonist. Both are poorly excreted in patients with renal failure. However, the metabolism of morphine was rapid when compared to the transfer of metabolites through the blood-brain barrier, which appears to be the limiting process. Because poor analgesia due to M-3-G's effect may occur in some patients after 1 or 2 days, a switch to other molecules should be considered.
Authors:
Jean Xavier Mazoit; Karin Butscher; Kamran Samii
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  105     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-20     Completed Date:  2007-07-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  70-8     Citation Subset:  AIM; IM    
Affiliation:
Univ Paris-Sud, Laboratoire d'Anesthésie UPRES 3540, Faculté de Médecine, Le Kremlin Bicêtre, France. jean-xavier.mazoit@u-psud.fr
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Female
Humans
Male
Metabolic Networks and Pathways / drug effects,  physiology
Middle Aged
Morphine / metabolism*,  pharmacology*,  therapeutic use
Morphine Derivatives / metabolism
Pain, Postoperative / drug therapy,  metabolism
Postoperative Period*
Chemical
Reg. No./Substance:
0/Morphine Derivatives; 20290-09-9/morphine-3-glucuronide; 20290-10-2/morphine-6-glucuronide; 57-27-2/Morphine

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