title: 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.
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 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.
authors.affiliation: Department of Anaesthesiology, Radboud University Medical Centre Nijmegen The Netherlands. HD.de.Boer@mzh.nl
authors.forename: H D
authors.initials: HD
authors.lastname: de Boer
authors.forename: J
authors.initials: J
authors.lastname: van Egmond
authors.forename: F
authors.initials: F
authors.lastname: van de Pol
authors.forename: A
authors.initials: A
authors.lastname: Bom
authors.forename: J J
authors.initials: JJ
authors.lastname: Driessen
authors.forename: L H D J
authors.initials: LH
authors.lastname: Booij
mesh_terms: 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*
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D000077123:Rocuronium