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-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.


CONCLUSIONS
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.
Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
Qinqin
Q
Yin
North Sichuan Medical College, Nanchong, Sichuan, P. R. China.
Jun
J
Li
Center for Drug Clinical Research, Shanghai University of Chinese Medicine, Shanghai, P. R. China.
Qingshan
Q
Zheng
North Sichuan Medical College, Nanchong, Sichuan, P. R. China.
Xiaolin
X
Yang
Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
Rong
R
Lv
Kunming Medical University, Kunming, Yunnan, P. R. China.
Longxiang
L
Ma
Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.|Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
Jin
J
Liu
Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.|Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
Tao
T
Zhu
Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.|Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
Wensheng
W
Zhang
D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000627:therapeutic use*; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D008962:Models, Theoretical; D009407:Nerve Block / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects; D016896:Treatment Outcome
D000779:Anesthetics, Local; C012647:QX-314; D008012:Lidocaine; D002045:Bupivacaine