Pharmacokinetic Profile of Liposome Bupivacaine Injection Following a Single Administration at the Surgical Site

Abstract

Local anaesthetics are often used as part of multimodal pain management techniques to manage postsurgical pain and lessen the need for opioid analgesics; however, the duration of action of traditional formulations of local anaesthetics is short. Liposome bupivacaine is a novel, multivesicular formulation designed for rapid absorption, prolonged release of bupivacaine, and analgesia following a single intra-operative administration into the surgical wound. This article provides a summary of the pharmacokinetic profile of liposome bupivacaine compared with bupivacaine HCl based on data compiled from four randomized, active- and placebo-controlled trials that included pharmacokinetic assessments following single administrations of study drug. Each study evaluated the safety, efficacy and pharmacokinetic profile of liposome bupivacaine in separate surgical populations (patients undergoing inguinal hernia repair, total knee arthroplasty, haemorrhoidectomy or bunionectomy). Pharmacokinetic parameters included maximum plasma drug concentration (C(max)), area under the curve (AUC) for plasma bupivacaine concentration over time extrapolated to infinity (AUC(∞)), time to observed C(max) (t(max)) and terminal elimination half-life of bupivacaine (t(½)). The studies assessed single administrations of liposome bupivacaine at dose levels ranging from 106 to 532 mg or bupivacaine HCl 100 to 150 mg or placebo (0.9 % sodium chloride) given locally via wound infiltration at the end of surgery prior to wound closure. Male and non-pregnant female patients (n = 253) aged ≥18 years, scheduled to undergo surgery as per the specific protocol for each study, were enrolled. Patient characteristics were stratified by liposome bupivacaine doses ≤266 mg and >266 mg, and bupivacaine HCl treatment arms. Pharmacokinetic parameters for liposome bupivacaine doses of 106, 266, 399 and 532 mg were compared. Plasma concentration versus time profiles were quantitatively similar across these four dose levels of liposome bupivacaine, with an initial peak occurring within 1 h after administration followed by a second peak about 12-36 h later. The overall incidence of adverse events was lower in the liposome bupivacaine ≤266-mg group than the liposome bupivacaine >266-mg and bupivacaine HCl groups (100- or 150-mg doses). In summary, liposome bupivacaine was well tolerated across the four studies and varied surgical models, and exhibited bimodal kinetics with rapid uptake observed during the first few hours and prolonged release through 96 h after administration.

Pain Control and Functional Milestones in Total Knee Arthroplasty: Liposomal Bupivacaine versus Femoral Nerve Block

“…Additionally, the observed decrease in narcotic consumption occurred during the first 2 days postoperatively, which could be explained by the reported window for clinical efficacy and pharmacokinetics reported for liposomal bupivacaine [13]. After approximately 72 hours, when the liposomal bupivacaine effect has worn off, the narcotic consumption in the two groups of patients was not statistically different.…”

“…During the inpatient stay, pain scores during 8-hour intervals, narcotic use, and physical therapy milestones were compared. Results With the numbers available, we detected no clinically important difference in pain scores throughout the hospital stay; however, patients treated with liposomal bupivacaine consumed very slightly less narcotics overall (96 ± 62 versus 84 ± 73 eq mg of morphine; [95% confidence interval, [11][12][13] Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. One of the authors (RI) received a grant and personal fees from Pacira Pharmaceuticals (Parsippany, NJ, USA).…”

The novel use of different bupivacaine preparations with combined regional techniques for postoperative pain management in non–opioid-based laparoscopic inguinal herniorrhaphy

“…6 However, this would only account for roughly 2.5 mg of bupivacaine HCl in a 133 mg LB injection per abdominal infiltration. Although it is reported that LB exhibits time-to-onset characteristics similar to traditional bupivacaine HCl in a cutaneous pain model, 7 our clinical experience in more invasive surgeries (total knee arthroplasty, total hip arthroplasty, colectomies, open inguinal herniorrhaphy, and ventral hernia repairs) have not found this to be true.…”

“…LB exhibits a bimodal release profile with an initial peak soon after administration, followed by a later peak (associated with release of the liposome-encapsulated bupivacaine) that occurs within 10 to 36 hours after administration. 8 From our clinical experience, an additional administration of bupivacaine HCl is required to bridge the onset of the second peak (10-36 hours after administration) of LB for clinically effective anesthesia. Though there are concerns over possible local anesthetic toxicity with supplementary bupivacaine HCl dosing, additional bupivacaine HCl -up to 50% of the total LB dosemay be administered without adverse effects.…”

Local bupivacaine for postoperative pain management in thyroidectomized patients: A prospective and controlled clinical study

“…Recently, the advent of a liposomal formulation of bupivacaine has provided more favorable pharmacokinetics that reduces the risk of amide-related toxicity and provides long-lasting postoperative analgesia (13,18,35,36). Potential risks and benefits of liposomal bupivacaine, a very recently approved formulation of bupivacaine, need to be elucidated for postoperative pain control (36,37).…”