SABER-Bupivacaine is an injectable (infiltration or needle-free instillation) solution formulated in a non-polymeric matrix comprised of the high viscosity, fully esterified sugar derivative, Sucrose Acetate IsoButyrate (SAIB). SABER-Bupivacaine is designed to alleviate post-surgical pain for 48 – 72 hours. This single dose study with IV infusion of bupivacaine and subcutaneous SABER-Bupivacaine was designed to characterize the pharmacokinetic properties of bupivacaine following SABER-Bupivacaine administration. On day 1, eight healthy male and female subjects received an IV infusion of bupivacaine for 4 hours (2 mg/hr). Following a washout period, the same subjects received 5 mL of SABER-Bupivacaine administered as a pair of subcutaneous trailing injections in the abdominal region. Periodic safety and serial blood samples were collected for 24 hours after the IV and for 120 hours post-subcutaneous administration. The plasma samples were analyzed for bupivacaine concentration using an LC/MS method with a detection limit of 1 ng/mL. Following subcutaneous administration, the mean (CV) maximum plasma bupivacaine concentrations were 638 ng/mL (58%) and the mean time to maximum concentration was 12 hours. The mean plasma concentration of bupivacaine at 72 hours following SABER-Bupivacaine administration was 224 ng/mL. Using the IV pharmacokinetic data, the subcutaneous plasma concentration time profile was deconvoluted to determine the in-vivo release rate of bupivacaine from the SABER matrix. The calculated in-vivo release was between 10 – 20 mg/hr for 24 – 48 hours post administration and declining gradually thereafter, closely mimicking the observed in-vitro release rate. Clinical studies in patients have shown the pharmacokinetics of SABER-Bupivacaine is dose linear between 2.5 to 7.5 mL. SABER-Bupivacaine appears to be well tolerated, providing sustained delivery of bupivacaine for 48 – 72 hours, in a dose linear fashion and has no initial burst or dumping of bupivacaine. Its utility as a long acting local analgesic is currently under investigation in a variety of surgical models.