Abstract
Background and Objective: Sugammadex facilitates rapid reversal of rocuronium- and vecuronium-induced neuromuscular blockade. This study aimed to evaluate the safety, tolerability and pharmacokinetics of high doses of sugammadex (up to 96 mg/kg) in healthy subjects.
Methods: In this randomized, double-blind, crossover, placebo-controlled, single-centre study, 13 healthy adults were scheduled to receive three single intravenous doses of sugammadex in ascending order (32, 64 and 96 mg/kg) and placebo (interspersed between sugammadex doses), each separated by a 1-week washout period. Subjects were randomized to one of four treatment sequences, receiving doses as constant rate infusions over 5 minutes. Safety was assessed by adverse events, 12-lead ECGs, vital signs, and blood and urine laboratory parameters; pharmacokinetics were evaluated from blood and urine sugammadex concentrations.
Results: Sugammadex was well tolerated in 12 of the 13 subjects, with adverse events being generally mild, of limited duration and more frequent at higher doses. The most common adverse event was dysgeusia; there were no serious adverse events. One subject was withdrawn from the study after experiencing several adverse events following first exposure to sugammadex, related to a probable hypersensitivity reaction to sugammadex. Pharmacokinetics were dose linear over the dose range studied (32–96 mg/kg), and 90–93% of the sugammadex dose was excreted unchanged in urine within 48 hours.
Conclusion: High doses of sugammadex (up to 96 mg/kg) were well tolerated in 12 of the 13 subjects. One male subject experienced several adverse events associated with a probable hypersensitivity reaction to sugammadex. Pharmacokinetics were dose linear over the range 32–96 mg/kg, with elimination predominantly via the renal route.
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Acknowledgements
This study was supported by MSD, Oss, the Netherlands. Pierre Peeters, Michiel van den Heuvel, Emiel van Heumen and Alex Zwiers are all employees of MSD (Oss, the Netherlands). Paul Passier and Jean Smeets were previously employees of MSD and are currently employed by Astellas (Leiderdorp, the Netherlands) and LAP&P Consultants BV (Leiden, the Netherlands), respectively. Thijs van Iersel, the Principal Investigator of the trial, was previously an employee of MSD, but was employed by Xendo (Groningen, the Netherlands) at the time of the start of the trial.
Pharmacokinetic calculations for this manuscript were performed by Dennis Doorstam (MSD, Oss, the Netherlands). Medical writing assistance was provided by Neil Venn (Prime Medica, Knutsford, UK) during the preparation of this manuscript.
The design and conduct of the study, as well as opinions on analysis, conclusions and interpretation of the study data, are the responsibility of the authors.
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Peeters, P.A.M., van den Heuvel, M.W., Heumen, E.v. et al. Safety, Tolerability and Pharmacokinetics of Sugammadex Using Single High Doses (Up to 96 mg/kg) in Healthy Adult Subjects. Clin. Drug Investig. 30, 867–874 (2010). https://doi.org/10.1007/BF03256915
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DOI: https://doi.org/10.1007/BF03256915