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

Abstract

Objective: To test the anesthetic effect of a bupivacaine liposome injectable suspension (BLIS), used in a multiple-dose manner for up to 5 consecutive days. Study design: Prospective, randomized, experimental study. Animals: A 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). Methods: Rats 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 A 14 gauge needle attached to an injection plug was used to puncture each vial once and was not removed; BLIS was withdrawn from the injection plug in a multiple-dose fashion.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. Results: Age 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 relevance: BLIS 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.