The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats
The quaternary lidocaine derivative (QX-314) in combination with bupivacaine can produce long-lasting nerve blocks in vivo, indicating potential clinical application. The aim of the study was to investigate the efficacy, safety, and the optimal formulation of this combination. QX-314 and bupivacaine...
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Published in | PloS one Vol. 12; no. 3; p. e0174421 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
23.03.2017
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | The quaternary lidocaine derivative (QX-314) in combination with bupivacaine can produce long-lasting nerve blocks in vivo, indicating potential clinical application. The aim of the study was to investigate the efficacy, safety, and the optimal formulation of this combination.
QX-314 and bupivacaine at different concentration ratios were injected in the vicinity of the sciatic nerve in rats; bupivacaine and saline served as controls (n = 6~10). Rats were inspected for durations of effective sensory and motor nerve blocks, systemic adverse effects, and histological changes of local tissues. Mathematical models were established to reveal drug-interaction, concentration-effect relationships, and the optimal ratio of QX-314 to bupivacaine.
0.2~1.5% QX-314 with 0.03~0.5% bupivacaine produced 5.8~23.8 h of effective nerve block; while 0.5% bupivacaine alone was effective for 4 h. No systemic side effects were observed; local tissue reactions were similar to those caused by 0.5% bupivacaine if QX-314 were used < 1.2%. The weighted modification model was successfully established, which revealed that QX-314 was the main active ingredient while bupivacaine was the synergist. The formulation, 0.9% QX-314 plus 0.5% bupivacaine, resulted in 10.1 ± 0.8 h of effective sensory and motor nerve blocks.
The combination of QX-314 and bupivacaine facilitated prolonged sciatic nerve block in rats with a satisfactory safety profile, maximizing the duration of nerve block without clinically important systemic and local tissue toxicity. It may emerge as an alternative approach to post-operative pain treatment. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceptualization: QY WZ.Data curation: QY J. Li RL LM QZ.Formal analysis: QY QZ.Funding acquisition: WZ J. Liu TZ.Investigation: QY J. Li RL LM.Methodology: QY TZ QZ.Project administration: QY WZ TZ.Resources: WZ TZ J. Liu.Software: QY QZ.Supervision: WZ J. Liu TZ XY.Validation: QY WZ TZ XY.Visualization: QY QZ.Writing – original draft: QY.Writing – review & editing: QY QZ WZ. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0174421 |