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BJA Advance Access published online on October 3, 2006
British Journal of Anaesthesia, doi:10.1093/bja/ael240
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted June 19, 2006

Laboratory Investigation

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{dagger}

H. D. de Boer 1 *, J. van Egmond 1, F. van de Pol 1, A. Bom 2, J. J. Driessen 1, and L. H. D. J. Booij 1

1 Department of Anaesthesiology, Radboud University Medical Centre Nijmegen, The Netherlands
2 Department of Pharmacology, Organon Newhouse, ML1 5SH, Scotland, UK

* To whom correspondence should be addressed.
H. D. de Boer, E-mail: HD.de.Boer{at}mzh.nl


  Abstract

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 µg kg-1 (about 1xED90) 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 µg 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.

Keywords: Sugammadex (Org 25969), reversal agent, rocuronium, neuromuscular block, time course of action.
{dagger}Declaration of interest. This study was supported by a grant from Organon. A.B. is employed by Organon and L.H.D.J.B. is a member of their scientific advisory board. H.D.B. is also working as staff anaesthesiologist at the Department of Anaesthesiology at the Martini Hospital Groningen, Groningen, The Netherlands.
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