J C Fréville1, G Dollo, P Le Corre, F Chevanne, R Le Verge. 1. Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes, France.
Abstract
PURPOSE: 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.
PURPOSE: 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.