Korean J Anesthesiol.  2013 Feb;64(2):143-151. 10.4097/kjae.2013.64.2.143.

The synergistic effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade

• Lee JH
• Lee SI
• Chung CJ
• Lee JH
• Lee SC
• Choi SR
• Oh JN
• Bae JY

• KMID: 1798228
• DOI: http://doi.org/10.4097/kjae.2013.64.2.143

Abstract

BACKGROUND
Gentamicin reduces acetylcholine release and clindamycin causes end-plate ion channel blockade. Because of these reasons, two drugs show muscular relaxant effect and potentiate the action of nondepolarizing neuromuscular agents. This study was intended to evaluate the effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade and the interaction between these drugs.
METHODS
Male Sprague-Dawley rats' phrenic nerves and diaphragms were installed in a bath containing Krebs solution. They were divided into three study groups. The first group was pre-treated with 0.1 (n = 3), 0.2 (n = 4) or 0.5 (n = 3) mM gentamicin and the tension was measured as the concentration of rocuronium was increased. The second group was experimented by increasing gentamicin on 0.25 (n = 5), 0.5 (n = 6) or 1.0 (n = 6) mM clindamycin. The final group was pre-treated with various combinations of gentamicin and clindamycin. The drug concentration was gradually increased until single twitch tension decreased by around 80%. Effective concentration was calculated using a probit model and interaction indices derived the Loewe additivity.
RESULTS
The administration of gentamicin and the combination of gentamicin and clindamycin enhanced rocuronium-induced neuromuscular blockade. At 0.2 and 0.5 mM gentamicin, synergistic interactions with rocuronium were observed. Likewise, at 0.5 and 1.0 mM clindamycin, synergistic interactions with gentamicin appeared. When all three drugs were combined, in the tetanic fade, all the groups except for those administered with 0.01 mM gentamicin and 0.25 mM clindamycin showed synergistic interactions.
CONCLUSIONS
This study demonstrate that gentamicin and clindamycin potentiated rocuronium induced neuromuscular blockade. Moreover, it was found that these drugs interacted synergistically.

Keyword

Clindamycin; Gentamicin; Interaction; Neuromuscular blockade; Rocuronium; Synergy

MeSH Terms

Acetylcholine
Androstanols
Baths
Clindamycin
Diaphragm
Gentamicins
Humans
Ion Channels
Isotonic Solutions
Male
Neuromuscular Agents
Neuromuscular Blockade
Phrenic Nerve
Refractory Period, Electrophysiological
Acetylcholine
Androstanols
Clindamycin
Gentamicins
Ion Channels
Isotonic Solutions
Neuromuscular Agents