Biphasic drug absorption from the epidural space of the dog may limit the utility of a slow release medium molecular weight hyaluronic acid-lidocaine ionic complex formulation

Anesthesia and Analgesia
M M DohertyW N Charman

Abstract

Previous epidural studies conducted in rabbits have described a viscous lidocaine-hyaluronate formulation (L-HA) that prolonged the duration of sensory blockade twofold and decreased the rate of drug absorption fourfold relative to a solution formulation. As further evaluation of the L-HA formulation required studies in a larger animal that more closely reflected the characteristic absorption kinetics observed in humans, a conscious dog model was used to functionally and kinetically evaluate the viscous formulation relative to lidocaine solution. In terms of the measured pharmacodynamic end point (loss of weight-bearing ability in hind legs), epidural administration of the L-HA formulation did not prolong the duration of action relative to lidocaine solution in spite of a markedly altered pharmacokinetic profile. For example, administration of L-HA reduced the mean plasma lidocaine Cmax value approximately 50% and increased the Tmax value approximately fivefold relative to lidocaine solution. However, the viscous L-HA formulation did cause a significant prolongation in the latency of onset (P < 0.001) relative to lidocaine solution. The dog exhibited "flip-flop" pharmacokinetics and absorption was biphasic after epidural admini...Continue Reading

References

Sep 1, 1975·British Journal of Anaesthesia·G T TuckerH Pandya
Jun 1, 1992·Anesthesia and Analgesia·T MashimoI Yoshiya
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Apr 1, 1993·Anaesthesia·D J Bihari, R W Chang

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Citations

May 11, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Franco David BattistiniRubén Hilario Manzo
Mar 17, 2004·International Journal of Pharmaceutics·Gilles DolloPascal Le Corre
Apr 29, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G DolloR Le Verge

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