PMID- 33237534
OWN - NLM
STAT- MEDLINE
DCOM- 20210414
LR  - 20210414
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 38
IP  - 1
DP  - 2021 Jan
TI  - Pharmacokinetics and Safety of INL-001 (Bupivacaine HCl) Implants Compared with 
      Bupivacaine HCl Infiltration After Open Unilateral Inguinal Hernioplasty.
PG  - 691-706
LID - 10.1007/s12325-020-01565-x [doi]
AB  - 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 INL-001 implants, each containing 100 mg 
      bupivacaine HCl (n = 34) or local infiltration of 0.25% 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.
FAU - Leiman, David
AU  - Leiman D
AD  - HD Research LLC, Houston, TX, USA. leimanmd@gmail.com.
AD  - University of Texas Health Science Center, Houston, TX, USA. leimanmd@gmail.com.
FAU - Niebler, Gwendolyn
AU  - Niebler G
AD  - Innocoll Inc, Newtown Square, PA, USA.
FAU - Minkowitz, Harold S
AU  - Minkowitz HS
AD  - HD Research LLC, Houston, TX, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03234374
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20201125
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (Anesthetics, Local)
RN  - Y8335394RO (Bupivacaine)
MH  - Anesthetics, Local
MH  - Bupivacaine
MH  - *Hernia, Inguinal/surgery
MH  - *Herniorrhaphy
MH  - Humans
MH  - Pain, Postoperative/drug therapy
MH  - Single-Blind Method
PMC - PMC7854444
OTO - NOTNLM
OT  - Bupivacaine HCl
OT  - Collagen-matrix implant
OT  - INL-001
OT  - Postsurgical pain
OT  - Xaracoll
EDAT- 2020/11/26 06:00
MHDA- 2021/04/15 06:00
PMCR- 2020/11/25
CRDT- 2020/11/25 12:18
PHST- 2020/09/22 00:00 [received]
PHST- 2020/11/07 00:00 [accepted]
PHST- 2020/11/26 06:00 [pubmed]
PHST- 2021/04/15 06:00 [medline]
PHST- 2020/11/25 12:18 [entrez]
PHST- 2020/11/25 00:00 [pmc-release]
AID - 10.1007/s12325-020-01565-x [pii]
AID - 1565 [pii]
AID - 10.1007/s12325-020-01565-x [doi]
PST - ppublish
SO  - Adv Ther. 2021 Jan;38(1):691-706. doi: 10.1007/s12325-020-01565-x. Epub 2020 Nov 
      25.