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Excerpt
Epidural anaesthesia using local anaesthetics is currently increasing for regional anaesthesia during routine surgery as well as for regional control of acute and chronic pain. However, local anaesthetics present a relative short duration of action and have potentially major side-effects (i.e. cardiac and neurological toxicity). Thus, there is a need for an improvement in their therapeutic index. This could be obtained by the development of drug-delivery systems that allow a controlled release of these drugs. Among the various ways of obtaining delivery systems, complex formation with the cyclodextrins (CDs) may provide interesting. Natural β-CDs are cyclic oligosaccharides containing seven α-1,4-linked glucopyranose units able to entrap many drugs in their hydrophobic cavities to form non-covalent inclusion compounds (Fig. 1)[1,2]. We demonstrated in an earlier study in rabbit an intensification and prolongation of epidural block when bupivacaine-β-CD was made into a complex with parenterally safe modified β-CDs as compared with bupivacaine alone [3]; similar results were obtained with sciatic nerve block [4].
The present correspondence reports the pharmacokinetics as well as a pharmacodynamics evaluation of a bupivacaine complex with sulphobutyl ether cyclodextrin derivatives (SBE7-β-CD) following epidural administration in another species, i.e. sheep. Bupivacaine hydrochloride (B-HCl) was used as control.
