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Dose safety and pharmacodynamics of subcutaneous bupivacaine in a novel extended-release microparticle formulation: A phase 1, dose-ascending study in male volunteers.
Jensen, Elisabeth Kjær; Bøgevig, Søren; Balchen, Torben; Springborg, Anders Holten; Royal, Mike Allan; Storgaard, Ida Klitzing; Lund, Trine Meldgaard; Møller, Kirsten; Werner, Mads Utke.
Afiliación
  • Jensen EK; Department of Anesthesia, Pain and Respiratory Support, Neuroscience Center, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
  • Bøgevig S; DanTrials, Zelo Phase 1 Unit, Copenhagen University Hospitals-Bispebjerg Hospital, Copenhagen, Denmark.
  • Balchen T; Department of Clinical Pharmacology, Copenhagen University Hospitals-Bispebjerg Hospital, Copenhagen, Denmark.
  • Springborg AH; DanTrials, Zelo Phase 1 Unit, Copenhagen University Hospitals-Bispebjerg Hospital, Copenhagen, Denmark.
  • Royal MA; Department of Anesthesia, Pain and Respiratory Support, Neuroscience Center, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
  • Storgaard IK; DanTrials, Zelo Phase 1 Unit, Copenhagen University Hospitals-Bispebjerg Hospital, Copenhagen, Denmark.
  • Lund TM; Liquidia Technologies, Morrisville, North Carolina, USA.
  • Møller K; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Werner MU; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Basic Clin Pharmacol Toxicol ; 134(5): 657-675, 2024 May.
Article en En | MEDLINE | ID: mdl-38482995
ABSTRACT
A novel microparticle-based extended-release local anaesthetic containing a bupivacaine/poly-lactic-co-glycolic acid (PLGA; LIQ865A) or plain bupivacaine (LIQ865B) was examined in a first-in-human trial. The objectives were to examine the dose safety/tolerability and pharmacodynamics. Randomized subcutaneous injections of LIQ865A (n = 16) or LIQ865B (n = 12) and diluent, contralaterally, were administered in a dose-ascending manner (150- to 600-mg bupivacaine). Subjects were admitted 24 h post-injection and followed for 30 days post-injection. The risk ratios (RRs; 95% CI) of erythematous reactions for LIQ865A versus diluent was 9.00 (1.81-52.23; P = 0.006) and for LIQ865B versus diluent 2.50 (0.69-9.94; P = 0.37). The RR for the development of hematomas (LIQ865A versus diluent) were 3.25 (1.52-8.16; P = 0.004) and 4.00 (0.72-24.89; P = 0.32) (LIQ865B versus diluent). Subcutaneous indurations persisting for 4-13 weeks were seen in 6/16 subjects receiving LIQ865A. One subject receiving LIQ865A (600-mg bupivacaine) developed intermittent central nervous system (CNS) symptoms of local anaesthetic systemic toxicity (85 min to 51 h post-injection) coinciding with plasma peak bupivacaine concentrations (490-533 ng/ml). Both LIQ865 formulations demonstrated dose-dependent hypoesthesia and hypoalgesia. The duration of analgesia ranged between 37 and 86 h. The overall number of local adverse events, however, prohibits clinical application without further pharmacological modifications.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bupivacaína / Analgesia Límite: Humans / Male Idioma: En Revista: Basic Clin Pharmacol Toxicol Asunto de la revista: FARMACOLOGIA / TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bupivacaína / Analgesia Límite: Humans / Male Idioma: En Revista: Basic Clin Pharmacol Toxicol Asunto de la revista: FARMACOLOGIA / TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido