Sugammadex sodium
Sugammadex (designation Org 25969, tradename Bridion) is an agent for reversal ofneuromuscular blockade by the agent rocuronium in general anaesthesia. It is the firstselective relaxant binding agent (SRBA) and was discovered at the Newhouse research site in Scotland. These scientists who discovered Sugammadex worked for the pharmaceutical company, Organon. Organon was acquired by Schering-Plough in 2007; Schering-Plough merged with Merck in 2009. Sugammadex is now owned and sold by Merck.
On January 3, 2008, Schering-Plough submitted a New Drug Application to the US Food and Drug Administration for sugammadex, but the FDA rejected the application on August 2008. It was approved for use in the European Union on July 29, 2008.
Sugammadex incapsulating a molecule of rocuronium
Sugammadex is a modified γ-cyclodextrin, with a lipophilic core and a hydrophilic periphery. This gamma cyclodextrin has been modified from its natural state by placing eight carboxyl thio ether groups at the sixth carbon positions. These extensions extend the cavity size allowing greater encapsulation of the rocuronium molecule. These negatively charged extensions electrostatically bind to the quaternary nitrogen of the target as well as contribute to the aqueous nature of the cyclodextrin. Sugammadex’s binding encapsulation of rocuronium is one of the strongest among cyclodextrins and their guest molecules. The rocuronium molecule (a modified steroid) bound within sugammadex’s lipophilic core, is rendered unavailable to bind to the acetylcholine receptor at theneuromuscular junction.
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Right: Space-filling model of a sugammadex sodium molecule in the same orientationSugammadex also has some affinity for other aminosteroid neuromuscular blocking agents such as vecuronium and pancuronium. Though sugammadex’s affinity for vecuronium is lower than its affinity for rocuronium, reversal of vecuronium is still effective because fewer vecuronium molecules are present in vivo for equivalent blockade. Vecuronium is approximately seven times more potent than rocuronium and overall requires fewer molecules to induce blockade. Sugammadex encapsulates with a 1:1 ratio and therefore will adequately reverse vecuronium as there are fewer molecules to bind compared to rocuronium. Shallow Pancuronium blockade has been successfully reversed by sugammadex in phase III clinical trials.
A study was carried out in Europe looking at its suitability in rapid sequence induction. It found that sugammadex provides a rapid and dose-dependent reversal of neuromuscular blockade induced by high-dose rocuronium.
A Cochrane systematic review on sugammadex has been recently published by Abrishami et al. This review article included 18 randomized controlled trials on the efficacy and safety of sugammadex. The trials included a total of 1321 patients. The review concluded that “sugammadex was shown to be more effective than placebo (no medication) or neostigmine in reversing muscle relaxation caused by neuromuscular blockade during surgery and is relatively safe. Serious complications occurred in less than 1% of the patients who received sugammadex. The results of this review article (especially the safety results) need to be confirmed by future trials on larger patient populations”.
