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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Complexation with HP-beta-CD could be a promising drug delivery system to improve the therapeutic index of bupivacaine.
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes, France.
J C
JC
Fréville
G
G
Dollo
P
P
Le Corre
F
F
Chevanne
R
R
Le Verge
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000042:Absorption / Q000187:drug effects; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003505:Cyclodextrins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers; D004347:Drug Interactions; D007268:Injections, Epidural; D008297:Male; D011817:Rabbits; D047392:beta-Cyclodextrins
D000779:Anesthetics, Local; D003505:Cyclodextrins; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002045:Bupivacaine