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Anesthesia and Pain Medicine 2009;4(1):5-10.
Published online January 30, 2009.
Comparative acute toxicity of quaternary ammonium lidocaine derivative QX-314 to lidocaine in mice
Sang Mook Lee, Kyu Don Chung, Yoon Suk Son, Sung Jun Yu, Keon Hee Ryu, Sang Hoon Lee, Hyun Sook Cho
Deparment of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. rae700@hanmail.net
Abstract
BACKGROUND
The current study examined the acute systemic toxicity of QX-314 that there have been few research results for this so far. In order to be useful as a drug, it must be shown to have minimal toxicities. Hence, we compared the CNS and cardiac toxicities of QX-314 to the conventional local anesthetic lidocaine.
METHODS
Acute toxicity was evaluated by determining the individual intravenous CD50 and LD50 of QX-314 and lidocaine. There were four doses for each LD50 determination and 8 animals per dose level. Animals were observed for several hours immediately following drug administration and recorded overt effects and fatalities. Both lidocaine and QX-314 were dissolved in saline. Lidocaine and QX-314 were diluted to 1, 2, 4, 6 and 0.5, 1, 2, 4%, respectively with saline and injected at the same volume to minimized cardiovascular effect.
RESULTS
The intravenous CD50 and LD50 were 12.7 and 14.1 mg/kg for QX-314 and 15.7 and 28.8 mg/kg for lidocaine. Electrocardiograms showed intraventricular block (widened QRS complex) at high doses of lidocaine compared to AV block (loss of QRS complex) at high concentrations of QX-314. There are no evidence that CNS toxicity led mouse to death.
CONCLUSIONS
QX-314 is about 1.5 times as toxic as lidocaine. Although QX-314 may still be useful clinically as a long-lasting local anesthetic, its safety relative to other available local anesthetics must be considered.
Key Words: acute toxicity, lidocaine, QX-314
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