Controlled systemic absorption and increased anesthetic effect of bupivacaine following epidural administration of bupivacaine-hydroxypropyl-β-cyclodextrin complex

To investigate the influence of complexation between bupivacaine and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the systemic absorption and on the pharmacodynamic effect of bupivacaine following epidural administration in a rabbit model. Bupivacaine and bupivacaine-HP-beta-CD complex were admin...

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Bibliographic Details
Published in:Pharmaceutical research 1996-10, Vol.13 (10), p.1576-1580
Main Authors: FREVILLE, J. C, DOLLO, G, LE CORRE, P, CHEVANNE, F, LE VERGE, R
Format: Article
Language:English
Subjects:
2-Hydroxypropyl-beta-cyclodextrin
Absorption - drug effects
Anesthetics, Local - administration & dosage
Anesthetics, Local - pharmacokinetics
Anesthetics. Neuromuscular blocking agents
Animals
beta-Cyclodextrins
Biological and medical sciences
Bupivacaine - administration & dosage
Bupivacaine - pharmacokinetics
Cyclodextrins - administration & dosage
Cyclodextrins - pharmacokinetics
Cyclodextrins - pharmacology
Drug Carriers
Drug Interactions
Injections, Epidural
Male
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Rabbits
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Summary:To investigate the influence of complexation between bupivacaine and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the systemic absorption and on the pharmacodynamic effect of bupivacaine following epidural administration in a rabbit model. Bupivacaine and bupivacaine-HP-beta-CD complex were administered according to a randomized and cross-over design in six rabbits chronically instrumented with an epidural catheter. The plasma concentrations of bupivacaine and the duration and intensity of the motor blockade were evaluated. Complexation with HP-beta-CD led to a decrease in the maximum plasma concentration of bupivacaine. Individual absorption kinetics evaluated by Loo-Riegelman absorption analysis indicated that systemic absorption resulted from two parallel first-order processes. Only the faster absorption phase was slowed by complexation with HP-beta-CD. The duration of the motor blockade was increased almost twice but the intensity was not modified. Complexation with HP-beta-CD could be a promising drug delivery system to improve the therapeutic index of bupivacaine.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1016000217550