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The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats

OBJECTIVE: 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. METHODS: QX...

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Autores principales: Yin, Qinqin, Li, Jun, Zheng, Qingshan, Yang, Xiaolin, Lv, Rong, Ma, Longxiang, Liu, Jin, Zhu, Tao, Zhang, Wensheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363931/
https://www.ncbi.nlm.nih.gov/pubmed/28334014
http://dx.doi.org/10.1371/journal.pone.0174421
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author Yin, Qinqin
Li, Jun
Zheng, Qingshan
Yang, Xiaolin
Lv, Rong
Ma, Longxiang
Liu, Jin
Zhu, Tao
Zhang, Wensheng
author_facet Yin, Qinqin
Li, Jun
Zheng, Qingshan
Yang, Xiaolin
Lv, Rong
Ma, Longxiang
Liu, Jin
Zhu, Tao
Zhang, Wensheng
author_sort Yin, Qinqin
collection PubMed
description OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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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spelling pubmed-53639312017-04-06 The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats Yin, Qinqin Li, Jun Zheng, Qingshan Yang, Xiaolin Lv, Rong Ma, Longxiang Liu, Jin Zhu, Tao Zhang, Wensheng PLoS One Research Article OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. Public Library of Science 2017-03-23 /pmc/articles/PMC5363931/ /pubmed/28334014 http://dx.doi.org/10.1371/journal.pone.0174421 Text en © 2017 Yin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yin, Qinqin
Li, Jun
Zheng, Qingshan
Yang, Xiaolin
Lv, Rong
Ma, Longxiang
Liu, Jin
Zhu, Tao
Zhang, Wensheng
The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats
title The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats
title_full The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats
title_fullStr The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats
title_full_unstemmed The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats
title_short The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats
title_sort quaternary lidocaine derivative qx-314 in combination with bupivacaine for long-lasting nerve block: efficacy, toxicity, and the optimal formulation in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363931/
https://www.ncbi.nlm.nih.gov/pubmed/28334014
http://dx.doi.org/10.1371/journal.pone.0174421
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