Complexation Of 50% Enantiomeric Excess (s75-r25) Bupivacaine With Cyclodextrins And Spinal Block Anesthesia In Rats [mistura Com Excesso Enantiomérico De 50% (s75-r25) De Bupivacaína Complexada Com Ciclodextrinas E Anestesia Por Via Subaracnóidea Em Ratos]

BACKGROUND AND OBJECTIVES: In order to prolong the action and reduce systemic toxicity, formulations of local anesthetic (LA) complexed with cyclodextrins (CD) have been developed. This study determined the physical-chemical characterization and evaluated the effects of inclusion complexes of racemic bupivacaine (S50-R50) and 50% enantiomeric excess (S75-R25) bupivacaine with hydroxypropil-beta-cyclodextrin (HP-β-CD) in rats, and comparing them with the solutions currently used in the clinical practice. METHODS: Inclusion complexation of S75-R25 with HP-β-CD (equimolar ratio 1:1) was characterized by phase-solubility studies varying the concentrations of HP-β-CD and the temperature. Affinity constants (K) for HP-β-CD and the thermodynamic parameters for complexation were determined. Motor and sensitive anesthesias were evaluated through the subarachnoid administration of the formulations in the concentration of 0.5%. RESULTS: Inclusion complexation was observed through the increase in aqueous solubility of LA in different temperatures and concentrations of HP-β-CD. The in vivo tests demonstrated that S50-R50 HP-β-CD and S75-R25 HP-β-CD reduced latency (p < 0.001) without changing the recovery time of the motor block, time for maximal effect, and total effect of the drugs. Besides, both formulations increased the intensity (1.5 times, p < 0.001) and prolonged the duration of analgesia compared to the free drugs. CONCLUSIONS: The complexes S50-R50 HP-β-CD and S75-R25 HP-β-CD potentiated the differential nervous block, and can be used to reduce the frequency of administration or the dose of the LA to induce the same effect. 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