title: Bupivacaine in microcapsules prolongs analgesia after subcutaneous infiltration in humans: a dose-finding study.
abstract: In this study, we examined the onset and duration of local analgesic effects of bupivacaine incorporated into biodegradable microcapsules (extended-duration local anesthetic; EDLA) administered as subcutaneous infiltrations in different doses in humans. In 18 volunteers, the skin on the medial calf was infiltrated with 10 mL of EDLA, and the opposite calf was infiltrated with 10 mL of aqueous bupivacaine (5.0 mg/mL) in a double-blinded, randomized manner. Three different concentrations of EDLA were tested (6.25, 12.5, and 25 mg/mL), with 6 subjects in each group. Pain responses to mechanical and heat stimuli and sensory thresholds (touch, warm, and cold detection thresholds) were examined by von Frey hairs and contact thermodes. Assessments were made before and 2, 4, 6, 8, 24, 48, 72, 96, and 168 h after the injections. Safety evaluations were performed daily for the first week and at 2 wk, 6 wk, and 6 mo after the injections. The time to maximum effects was significantly shorter for aqueous bupivacaine (2-6 h) than for EDLA (4-24 h), but there were no significant differences between the maximum effects of EDLA and aqueous bupivacaine. From 24 to 96 h after the injections, EDLA was significantly more efficient than aqueous bupivacaine for all variables, and significant effects of EDLA were demonstrated for at least 96 h for all variables. In general, a dose-response gradient was seen in the EDLA group for 5 of 7 variables when the curves expressing effect over time for the different concentrations were evaluated. No serious side effects were observed for up to 6 mo after administration. In conclusion, bupivacaine incorporated in microcapsules provided analgesia for 96 h after subcutaneous infiltration.
authors.affiliation: Department of Surgical Gastroenterology 435, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark. henrik.kehlet@hh.hosp.dk
authors.forename: Juri L
authors.initials: JL
authors.lastname: Pedersen
authors.forename: Jesper
authors.initials: J
authors.lastname: Lillesø
authors.forename: Niels A
authors.initials: NA
authors.lastname: Hammer
authors.forename: Mads U
authors.initials: MU
authors.lastname: Werner
authors.forename: Kathrine
authors.initials: K
authors.lastname: Holte
authors.forename: Peter G
authors.initials: PG
authors.lastname: Lacouture
authors.forename: Henrik
authors.initials: H
authors.lastname: Kehlet
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000698:Analgesia; D000779:Anesthetics, Local / Q000008:administration & dosage*; D002045:Bupivacaine / Q000008:administration & dosage*; D002214:Capsules; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D002214:Capsules; D002045:Bupivacaine