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

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.