Safety, tolerability and pharmacokinetics of sugammadex using single high doses (up to 96 mg/kg) in healthy adult subjects: a randomized, double-blind, crossover, placebo-controlled, single-centre study.
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 One subject was withdrawn from the study after experiencing several adverse events following first exposure to sugammadex, related to a probable hypersensitivity reaction to sugammadex.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.


CONCLUSIONS
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.
Peeters
Pierre A M
PA
Early Stage Development, MSD, Oss, the Netherlands. pierre.peeters2@merck.com
van den Heuvel
Michiel W
MW
van Heumen
Emiel
E
Passier
Paul C C M
PC
Smeets
Jean M W
JM
van Iersel
Thijs
T
Zwiers
Alex
A
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D015990:Placebo Effect; D000077122:Sugammadex; D016896:Treatment Outcome; D047408:gamma-Cyclodextrins / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
D009465:Neuromuscular Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex
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