PMID- 22266897
OWN - NLM
STAT- MEDLINE
DCOM- 20120921
LR  - 20190109
IS  - 1532-8651 (Electronic)
IS  - 1098-7339 (Linking)
VI  - 37
IP  - 2
DP  - 2012 Mar-Apr
TI  - Bupivacaine extended-release liposome injection exhibits a favorable cardiac 
      safety profile.
PG  - 145-51
LID - 10.1097/AAP.0b013e31823d0a80 [doi]
AB  - BACKGROUND AND OBJECTIVES: Bupivacaine extended-release liposome injection is an 
      investigational local analgesic intended for use in postsurgical pain management. 
      In recognition of the incompletely characterized association of bupivacaine use 
      and cardiac effects, this article reviews the cardiac safety profile of this 
      novel formulation of bupivacaine. METHODS: Findings from paired 
      electrocardiograms (ECGs), corresponding pharmacokinetic assessments, and 
      cardiovascular adverse events (AEs) in a phase 2, randomized, double-blind, 
      dose-ranging study of bupivacaine extended-release (150, 300, 450, or 600 mg) or 
      bupivacaine HCl 150 mg with epinephrine administered intraoperatively via wound 
      infiltration in patients undergoing total knee arthroplasty (n = 138), were 
      assessed for potential causality. Results from 4 phase 1 bupivacaine 
      extended-release studies that also obtained ECG and/or Holter monitor findings (n 
      = 169) were assessed. In addition, incidences of cardiovascular AEs reported 
      across 10 bupivacaine extended-release wound infiltration studies (n = 1459) were 
      pooled and assessed. RESULTS: In the phase 2 study, mean change from baseline in 
      QRS duration and QTcF duration across dose levels of bupivacaine extended-release 
      was similar (range, -1 to +4 milliseconds and -7 to -10 milliseconds) compared 
      with bupivacaine HCl (-1 millisecond and -6 milliseconds). Mean change from 
      baseline in heart rate, PR interval, and QRS interval was similar between 
      treatment groups as well. No clinically relevant ECG changes or cardiac AEs with 
      bupivacaine extended-release were observed in the other clinical studies. 
      CONCLUSIONS: A focused assessment of ECG data from a phase 2 study and cardiac 
      findings/AEs data from other studies in the bupivacaine extended-release 
      development program did not reveal any cardiac safety issues.
FAU - Bergese, Sergio D
AU  - Bergese SD
AD  - Department of Anesthesiology, Ohio State University, Columbus, OH 43210, USA. 
      sergio.bergese@osumc.edu
FAU - Onel, Erol
AU  - Onel E
FAU - Morren, Michael
AU  - Morren M
FAU - Morganroth, Joel
AU  - Morganroth J
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - England
TA  - Reg Anesth Pain Med
JT  - Regional anesthesia and pain medicine
JID - 9804508
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Liposomes)
RN  - Y8335394RO (Bupivacaine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Bupivacaine/*administration & dosage/*adverse effects
MH  - Delayed-Action Preparations/administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Electrocardiography/*drug effects
MH  - Female
MH  - Heart Diseases/chemically induced/*epidemiology
MH  - Humans
MH  - Liposomes
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Young Adult
EDAT- 2012/01/24 06:00
MHDA- 2012/09/22 06:00
CRDT- 2012/01/24 06:00
PHST- 2012/01/24 06:00 [entrez]
PHST- 2012/01/24 06:00 [pubmed]
PHST- 2012/09/22 06:00 [medline]
AID - 10.1097/AAP.0b013e31823d0a80 [doi]
PST - ppublish
SO  - Reg Anesth Pain Med. 2012 Mar-Apr;37(2):145-51. doi: 
      10.1097/AAP.0b013e31823d0a80.