Document Detail

Sustained-release morphine for epidural analgesia in rats.
MedLine Citation:
PMID:  8712449     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Epidural opioid analgesia often requires either continuous infusion or repeated injections, which are inconvenient for patients, increase risk of infection, and consume expensive physician and nursing time. In addition, potential respiratory depression is a major safety concern. The authors studied whether a single dose of epidurally administered, sustained-release morphine could prolong analgesia and reduce toxic effects in rats. METHODS: Sustained-release morphine (DTC401) was prepared by encapsulating morphine sulfate in DepoFoam (Dep. Tech, San Diego, CA), a lipid-based, sustained-release drug delivery system. A standard hot-plate test for analgesia, pulse oximetry for hemoglobin oxygen saturation, corneal-reflex loss, and incidence of catalepsy were used to assess efficacy and toxicities. Cerebrospinal fluid and serum pharmacokinetic studies were performed after a single epidural dose, using a commercially available radioimmunoassay kit. RESULTS: Single epidural doses of DTC401 resulted in equivalent onset time to peak analgesia but significantly prolonged analgesia compared with morphine sulfate. Hemoglobin oxygen saturation was decreased minimally, and the incidences of catalepsy and corneal-reflex loss were minimal, even at large doses of DTC401. In contrast, the larger doses of morphine sulfate significantly decreased hemoglobin oxygen saturation, and caused catalepsy and loss of the corneal-reflex. The Cmax for DTC401 was 32% in cerebrospinal fluid and 6% in serum, relative to morphine sulfate. The terminal half-life for DTC401 was increased 32 fold in the cerebrospinal fluid compared with morphine sulfate. CONCLUSIONS: A single epidural dose of DTC401, compared with morphine sulfate, prolonged duration of analgesia, with minimal supraspinal toxic effects, in rats.
T Kim; S Murdande; A Gruber; S Kim
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  85     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-09-12     Completed Date:  1996-09-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  331-8     Citation Subset:  AIM; IM    
DepoTech Corporation, San Diego, California 92121, USA.
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MeSH Terms
Analgesia, Epidural / methods*
Catheterization / methods
Delayed-Action Preparations
Morphine / administration & dosage*,  pharmacokinetics,  toxicity
Nociceptors / drug effects
Rats, Sprague-Dawley
Reg. No./Substance:
0/Delayed-Action Preparations; 57-27-2/Morphine

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