Time course of action of sugammadex (Org 25969) on rocuronium-induced block in the Rhesus monkey, using a simple model of equilibration of complex formation.
BACKGROUND
Reversal of neuromuscular block can be accomplished by chemical encapsulation of rocuronium by sugammadex (Org 25969), a synthetic gamma-cyclodextrin derivative. The present study determined the time course of the reversal action of sugammadex on rocuronium-induced block in the anaesthetized Rhesus monkey using train-of-four stimulation.


METHODS
A bolus injection of rocuronium 100 microg kg(-1) (about 1xED(90)) was given to determine the degree of neuromuscular block reached by this dose. After complete spontaneous recovery, a rapid bolus injection of sugammadex, 1 mg kg(-1), was given and at different time intervals (15, 30 or 60 min, in three different experiments) the effect of another rocuronium bolus injection of 100 microg kg(-1) was determined.


RESULTS
Injection of the first dose of rocuronium resulted in a mean neuromuscular block (depression of first twitch) of 93 (SEM=1.6)%. Fifteen minutes after injection of sugammadex the same rocuronium dose resulted in 17% (SEM=5.6) block. After 30 and 60 min these maximum blocks amounted to 49% (SEM=7.6) and 79% (SEM=4.2), respectively. The estimated half-life of sugammadex in Rhesus monkey is 30 (SEM=4.9) min.


CONCLUSIONS
The half-life of sugammadex (Org 25969), a new fast and efficient reversal agent for rocuronium-induced block, is relatively short in the Rhesus monkey, implying the possibility to perform neuromuscular block by rocuronium shortly after reversal of a prior block. In translation to the human situation differences in rocuronium sensitivity and kinetics should be taken into account.
de Boer
H D
HD
Department of Anaesthesiology, Radboud University Medical Centre Nijmegen The Netherlands. HD.de.Boer@mzh.nl
van Egmond
J
J
van de Pol
F
F
Bom
A
A
Driessen
J J
JJ
Booij
L H D J
LH
D000732:Androstanols / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D005260:Female; D006207:Half-Life; D008253:Macaca mulatta; D008954:Models, Biological; D019148:Neuromuscular Blockade; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000077123:Rocuronium; D000077122:Sugammadex; D013997:Time Factors; D047408:gamma-Cyclodextrins / Q000493:pharmacokinetics / Q000494:pharmacology*
D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D000077123:Rocuronium