CONTROLLED SYSTEMIC ABSORPTION AND INCREASED ANESTHETIC EFFECT OF BUPIVACAINE FOLLOWING EPIDURAL ADMINISTRATION OF BUPIVACAINE-HYDROXYPROPYL-BETA-CYDODEXTRIN COMPLEX

Purpose. To investigate the influence of complexation between bupivaca ine and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the systemic a bsorption and on the pharmacodynamic effect of bupivacaine following e pidural administration in a rabbit model, Methods. Bupivacaine and bup ivacaine-HP-beta-CD complex were administered according to a randomize d and cross-over design in six rabbits chronically instrumented with a n 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 c oncentration of bupivacaine. Individual absorption kinetics evaluated by Loo-Riegelman absorption analysis indicated that systemic absorptio n resulted from two parallel first-order processes, Only the faster ab sorption phase was slowed by complexation with HP-beta-CD. The duratio n of the motor blockade was increased almost twice but the intensity w as not modified. Conclusions. Complexation with HP-beta-CD could be a promising drug delivery system to improve the therapeutic index of bup ivacaine.