Comparison of bupivacaine concentrations in local tissue from three extended-release formulations in a pig incision...

This study measured bupivacaine distribution in subcutaneous (SC) tissue and skin after administration of the commercially available extended-release local anesthetics ERLAs liposomal bupivacaine (Lip-Bupi) and polyorthoester bupivacaine-meloxicam (POE-Bupi-Mel), an investigational temperature-responsive gel formulation (SBG004) by subcutaneous (SC) injection or wound filling (WF), and 0.25% bupivacaine HCl. Each ERLA was administered to six skin and muscle incisions in pigs surviving for 24, 48, or 72 h. Samples of skin or SC tissue representing 2 mm intervals from the incision were analyzed for bupivacaine concentration. Average bupivacaine concentration in each tissue within 10 mm of the incision ([BUPI]_SC,10mm or [BUPI]_skin,10mm) was compared between formulations. SBG004 SC resulted in higher [BUPI]_SC,10mm versus each other formulation at each time point (P < 0.01). Average [BUPI]_SC,10mm for SBG004 SC was 15 to 52-fold greater than Lip-Bupi and at least 64-fold greater than POE-Bupi-Mel (at 72 h: SBG004 SC 1,250 ± 580 µg/g; Lip-Bupi 24 ± 28 µg/g; POE-Bupi-Mel 20 ± 21 µg/g). Concentration differences in skin were similar but of a lower magnitude. The results indicate that injection in surgical wound margins and remaining in situ throughout the duration of release contribute to sustaining higher local anesthetic concentrations in tissue.