Pharmacokinetics and Safety of INL-001 (Bupivacaine HCl) Implants Compared with Bupivacaine HCl Infiltration After Open
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ORIGINAL RESEARCH
Pharmacokinetics and Safety of INL-001 (Bupivacaine HCl) Implants Compared with Bupivacaine HCl Infiltration After Open Unilateral Inguinal Hernioplasty David Leiman . Gwendolyn Niebler . Harold S. Minkowitz
Received: September 22, 2020 / Accepted: November 7, 2020 Ó The Author(s) 2020
ABSTRACT Introduction: Surgical site infiltration with bupivacaine HCl results in short-lived analgesia for postsurgical pain and carries the risk of systemic bupivacaine toxicity due to accidental intravascular injection. INL-001 is a bupivacaine HCl collagen-matrix implant that provides extended delivery of bupivacaine directly at the site and avoids the risk of accidental injection. Here, we examine the pharmacokinetic (PK) and safety profile of INL-001 placement during unilateral open inguinal hernioplasty. Methods: This multicenter, single-blind study (NCT03234374) enrolled patients undergoing open inguinal hernioplasty to receive three INL001 implants, each containing 100 mg bupivacaine HCl (n = 34) or local infiltration of 0.25% Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12325020-01565-x) contains supplementary material, which is available to authorized users. D. Leiman (&) H. S. Minkowitz HD Research LLC, Houston, TX, USA e-mail: [email protected] D. Leiman University of Texas Health Science Center, Houston, TX, USA G. Niebler Innocoll Inc, Newtown Square, PA, USA
bupivacaine HCl 175 mg (n = 16). Acetaminophen was provided in the postsurgical period and supplemented by opioids for breakthrough pain, as needed. PK blood samples were taken before surgery and up to 96 h after drug administration. Results: INL-001 demonstrated a prolonged rate of absorption and clearance of bupivacaine compared with 0.25% bupivacaine HCl 175 mg, as demonstrated by a longer time to peak plasma concentration and terminal elimination half-life. Peak plasma concentration with INL-001 300 mg was comparable to bupivacaine HCl 175 mg and well below levels associated with systemic bupivacaine toxicity. The most common adverse events (AEs) in both groups were associated with general anesthesia and the postsurgical setting. No AE was related to the implant, including those associated with wound healing. Conclusions: These findings demonstrate that INL-001 provides immediate and extended delivery of bupivacaine and is well tolerated in patients undergoing open inguinal hernioplasty with no adverse effect on wound healing. Trial registration: Clinicaltrials.gov identifier, NCT03234374. Keywords: Bupivacaine HCl; Collagen-matrix implant; INL-001; Postsurgical pain; Xaracoll
Adv Ther
DIGITAL FEATURES Key Summary Points Why carry out this study? Patients undergoing open inguinal hernia repair experience acute postsurgical pain. Use of opioids to control postsurgical pain has inherent risks; pain relief following surgical site infiltration of bupivacaine HCl is relatively short lived, has a risk of accidental intravascular administration, and may result in subsequent systemic bupivac
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