Document Detail

Population pharmacokinetic-pharmacodynamic modeling of epidural anesthesia.
MedLine Citation:
PMID:  18813046     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: In previous studies, the authors reported on the absorption and disposition kinetics of levobupivacaine and ropivacaine. The current study was designed to develop a population pharmacokinetic-pharmacodynamic model capable of linking the kinetic data to the analgesic effects of these local anesthetics (i.e., sensory neural blockade). METHODS: A disposition compartmental model was fitted to concentration data of the intravenously administered deuterium-labeled anesthetics, and a model consisting of two parallel absorption compartments and the identified disposition compartments was fitted to concentration data of the concomitantly epidurally administered unlabeled anesthetics. The epidural segments were modeled by individual central and peripheral absorption compartments and effect sites, which were fitted to the simultaneously acquired pinprick data. A covariate model incorporated the effects of age. RESULTS: The threshold for epidural anesthesia increased from the lower to the higher segments. The central effect compartment equilibration half-lives were approximately 15 min for levobupivacaine and 25 min for ropivacaine. For levobupivacaine, age reduced the equilibration half-lives at all segments; for ropivacaine, age increased the anesthetic sensitivity at segments T12 and higher. CONCLUSIONS: A population pharmacokinetic-pharmacodynamic model was developed that quantitatively described sensory blockade during epidural anesthesia, including the effects of age. The model may be useful to individualize dose requirements, to predict the time course of sensory blockade, and to study new local anesthetics.
Erik Olofsen; Antonius G L Burm; Mischa J G Simon; Bernadette Th Veering; Jack W van Kleef; Albert Dahan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anesthesiology     Volume:  109     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-24     Completed Date:  2008-10-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  664-74     Citation Subset:  AIM; IM    
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
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MeSH Terms
Age Factors
Amides / pharmacokinetics*,  pharmacology
Anesthesia, Epidural*
Anesthetics, Local / pharmacokinetics*,  pharmacology*
Bupivacaine / analogs & derivatives,  pharmacokinetics,  pharmacology
Middle Aged
Models, Biological
Reg. No./Substance:
0/Amides; 0/Anesthetics, Local; 0/levobupivacaine; 2180-92-9/Bupivacaine; 84057-95-4/ropivacaine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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