Impact of volume expansion on the efficacy and pharmacokinetics of liposome bupivacaine

Abstract: Liposome bupivacaine is a prolonged-release liposomal formulation of bupivacaine indicated for single-dose infiltration into the surgical site to produce postsurgical analgesia of longer duration than traditional local anesthetics. This review summarizes the available data on how volume expansion may impact the analgesic efficacy of liposome bupivacaine. The Phase II and III clinical studies that involved surgical site administration of liposome bupivacaine at various concentrations in different surgical settings revealed no apparent concentration–efficacy relationship. A single-center, prospective study comparing the efficacy of transversus abdominis plane infiltration with liposome bupivacaine administered in a lower (266 mg/40 mL) vs a higher (266 mg/20 mL) dose concentration in subjects undergoing robotic-assisted laparoscopic prostatectomy also reported similar postsurgical pain intensity scores and opioid usage in both treatment groups. The pharmacokinetic profile of liposome bupivacaine following subcutaneous injections in rats was unaltered by differences in drug concentration, dose, or injection volume within the ranges tested. Volume expansion of liposome bupivacaine to a total volume of 300 mL or less does not appear to impact its clinical efficacy or pharmacokinetic profile, thus allowing flexibility to administer the formulation across a wide range of diluent volumes. Keywords: pain, analgesia, liposome bupivacaine, dose, concentration, dilution