Dose safety and pharmacodynamics of subcutaneous bupivacaine in a novel extended-release microparticle formulation: A phase 1, dose-ascending study in male volunteers
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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.
In: Basic & clinical pharmacology & toxicology, Vol. 134, No. 5, 2024, p. 657-675.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Dose safety and pharmacodynamics of subcutaneous bupivacaine in a novel extended-release microparticle formulation
T2 - A phase 1, dose-ascending study in male volunteers
AU - Jensen, Elisabeth Kjær
AU - Bøgevig, Søren
AU - Balchen, Torben
AU - Springborg, Anders Holten
AU - Royal, Mike Allan
AU - Storgaard, Ida Klitzing
AU - Lund, Trine Meldgaard
AU - Møller, Kirsten
AU - Werner, Mads Utke
N1 - © 2024 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1111/bcpt.13998
DO - 10.1111/bcpt.13998
M3 - Journal article
C2 - 38482995
VL - 134
SP - 657
EP - 675
JO - Basic and Clinical Pharmacology and Toxicology
JF - Basic and Clinical Pharmacology and Toxicology
SN - 1742-7835
IS - 5
ER -
ID: 385895554