Evaluation of bupivacaine liposome injectable suspension efficacy in single-use vials over five days of multiple use

Abstract

ObjectiveTo test the anesthetic effect of a bupivacaine liposome injectable suspension (BLIS), used in a multiple-dose manner for up to 5 consecutive days. Study designProspective, randomized, experimental study. AnimalsA total of 30 male and female Sprague–Dawley rats (Rattus norvegicus), aged 97 (75–130) days and weighing 337.2 (219.6–465.9) g, mean (range). MethodsRats were assigned to one of five BLIS vial groups, in which drug was administered from a newly opened vial or 1, 2, 3 and 4 days after the vial was opened. The vials were refrigerated between uses. A 14 gauge needle attached to an injection plug was used to puncture each vial once and was not removed; BLIS was withdrawn from the injection plug in a multiple-dose fashion. A dose rate of 0.4 mL kg−1 was administered subcutaneously into the left pelvic limb paw. Antinociception was evaluated using a paw pressure test on both injected and uninjected paws before (time 0, baseline) and 1, 24, 48 and 72 hours after injection. ResultsAge of BLIS vial had no significant effect on anesthetic efficacy (p = 0.97). Across all groups, paw withdrawal latency averaged 5.23 ± 0.24 seconds at baseline (before BLIS injection), increased to 16.45 ± 0.65 seconds at 1 hour after BLIS injection, declined to 7.50 ± 0.76 seconds at 24 hours after BLIS injection, and further declined thereafter (p < 0.001). There was no significant change in paw withdrawal latency in the uninjected paw over time. Conclusions and clinical relevanceBLIS single-use vials retained efficacy when used up to 5 days in a multiple-dose fashion. Because anesthetic effects declined substantially after 24 hours, multimodal pain management remains important for providing analgesia care.