Abstract
Purpose. To investigate the influence of complexation between bupivacaine and hydroxypropyl-β-cyclodextrin (HP-β-CD) on the systemic absorption and on the pharmacodynamic effect of bupivacaine following epidural administration in a rabbit model.
Methods. Bupivacaine and bupivacaine-HP-β-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-β-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-β-CD. The duration of the motor blockade was increased almost twice but the intensity was not modified.
Conclusions. Complexation with HP-β-CD could be a promising drug delivery system to improve the therapeutic index of bupivacaine.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
B. G. Covino and D. H. Lambert, In P. G. Barash, B. F. Cullen and R. K. Stoelting (Eds), Clinical anesthesia, J. B. Lippincott, Philadelphia, 92, pp. 809–840.
T. H. Stanley. Anaesthesiology, 38:665–668 (1988).
L. Langerman, E. Golomb and S. Benita, Anesthesiology. 74:105–107 (1991).
T. Mashimo, I. Uchida, M. Pak, A. Shibata, S. Nishimura, Y. Inagaki and I. Yoshida, Anesth. Analg., 74:827–834 (1992).
M. M. Doherty, P. J. Hughes, N. V. Korszniak and W. N. Charman, Anesth. Analg. 80:740–746 (1995).
P. Le Corre, J. P. Estèbe, F. Chevanne, Y. Mallédant and R. Le Verge, J. Pharm. Sci. 84:75–78 (1995).
G. Dollo, P. Le Corre, F. Chevanne and R. Le Verge, Int. J. Pharm. 136:165–174 (1996).
J. Jang, T. L. Yaksh and H. F. Hill, J. Pharmacol. Exp. Ther. 261:592–600 (1992).
T. F. Meert, P. Putteman and J. Peeters, Drug Dev. Res. 28:28–37 (1993).
M. E. Brewster, J. W. Simpkins, M. Singhhora, W. C. Stern and N. Bodor, J. Parenter. Sci. Technol. 43:231–240 (1989).
R. A. Rajewski, G. Traiger, J. Bresnahan, P. Jaberaboansari, V. J. Stella and D. O. Thompson, J. Pharm. Sci. 84:927–932 (1995).
J. M. Malinowsky, J. M. Bernard, P. Le Corre, J. B. Dumand, J. Y. Lepage JY, R. Le Verge and R. Souron, Anesth. Analg. 81:519–524 (1995).
P. Le Guevello, P. Le Corre, F. Chevanne and R. Le Verge, J. Chromatogr. 622:284–290 (1993).
H. G. Boxenbaum, S. Riegelman and R. M. Elashoff, J. Pharmacokin. Biopharm. 2:123–148 (1974).
M. Gibaldi and D. Perrier, Pharmacokinetics, 2nd ed.; Marcel Dekker, New York, 1982.
A. G. L. Burm, Clin. Pharmacokin. 16:283–311 (1989).
A. G. L. Burm, N. P. E. Vermeulen, J. W. Van Kleef, A. G. De Boer and J. Spierdijk, Clin. Pharmacokin. 13:191–203 (1987).
T. F. Meert and W. Melis, Acta Anaesth. Belg. 43:79–89 (1992).
C. M. Bernards, J. Pharm. Sci. 83:620–622 (1994).
F.-Y. Liu, D. O. Kildsig and A. K. Mitra, Pharm. Res. 9:1671–1672 (1992).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fréville, J.C., Dollo, G., Le Corre, P. et al. Controlled Systemic Absorption and Increased Anesthetic Effect of Bupivacaine Following Epidural Administration of Bupivacaine-Hydroxypropyl-β-Cyclodextrin Complex. Pharm Res 13, 1576–1580 (1996). https://doi.org/10.1023/A:1016000217550
Issue Date:
DOI: https://doi.org/10.1023/A:1016000217550