title: Time to onset of analgesia following local infiltration of liposome bupivacaine in healthy volunteers: a randomized, single-blind, sequential cohort, crossover study.
abstract: OBJECTIVE
  Bupivacaine liposome injectable suspension is a novel, prolonged-release formulation of bupivacaine. The time to onset of analgesia following an injection of liposome bupivacaine compared with placebo (normal saline) was investigated using a novel incisional pain model. Bupivacaine HCl was used as a positive control, compared with placebo to verify the validity of the study.
  
  
  METHODS
  In this Phase 1, single-blind, crossover study, healthy volunteers (n = 132) were randomized to four sequential cohorts to receive subcutaneous normal saline in one arm and either liposome bupivacaine 40 mg or bupivacaine HCl 7.5 mg in the other. At 30, 15, 5, and 2 minutes after study drug administration for Cohorts 1 - 4 respectively, an incision was made in each arm and 18% acetic acid solution was applied to elicit pain. The primary outcome measure was a subject's assessment of pain intensity on a 100 mm visual analog scale.
  
  
  RESULTS
  Statistically significant differences in pain intensity scores between liposome bupivacaine and normal saline were observed at 30, 15, 5, and 2 minutes postdose; similar findings were reported for bupivacaine HCl vs. normal saline. Both liposome bupivacaine and bupivacaine HCl were well tolerated and achieved > 30% pain reduction, normalized to placebo, within 5 minutes.
  
  
  CONCLUSIONS
  These results indicate that liposome bupivacaine offers time to onset characteristics similar to traditional bupivacaine HCl: clinically meaningful analgesia within 2 minutes after administration and substantial analgesia by 5 minutes.
authors: The Ohio State University College of Medicine, Department of Pharmacology, Division of Clinical Pharmacology, Columbus, OH 43210, USA. apseloff.1@osu.edu
authors: Glen
authors: G
authors: Apseloff
authors: Erol
authors: E
authors: Onel
authors: Gary
authors: G
authors: Patou
mesh_terms: D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000009:adverse effects; D002045:Bupivacaine / Q000008:administration & dosage* / Q000009:adverse effects; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009820:Ohio; D010146:Pain / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D016037:Single-Blind Method; D013997:Time Factors; D055815:Young Adult
chemical_list: D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D008081:Liposomes; D002045:Bupivacaine