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

• Published in: PloS one Vol. 12; no. 3; p. e0174421
• Main Authors: Yin, Qinqin, Li, Jun, Zheng, Qingshan, Yang, Xiaolin, Lv, Rong, Ma, Longxiang, Liu, Jin, Zhu, Tao, Zhang, Wensheng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.03.2017; Public Library of Science (PLoS)
• Subjects: Analysis; Anesthesia; Anesthesiology; Anesthetics, Local - administration & dosage; Animal tissues; Animals; Biocompatibility; Biology and Life Sciences; Bupivacaine; Bupivacaine - administration & dosage; Bupivacaine - therapeutic use; Care and treatment; Critical care; Dosage and administration; Drug dosages; Drug interactions; In vivo methods and tests; Laboratories; Lidocaine; Lidocaine - administration & dosage; Lidocaine - analogs & derivatives; Male; Mathematical models; Medicine; Medicine and Health Sciences; Models, Theoretical; Musculoskeletal system; Nerve Block - methods; Neurosciences; Optimization; Pain; Quaternary; Rats; Rats, Sprague-Dawley; Safety; Sciatic nerve; Sciatic Nerve - drug effects; Side effects; Thrombosis; Toxicity; Treatment Outcome; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174421

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.