Cyclodextrins
➧ The starting point for encapsulating agents that used since 1953 as solubilizing agents and form low-affinity complexes with lipophilic drugs.
➧ γ-cyclodextrin: 8 sugar molecules forming a rigid ring with a central lipophilic cavity.
➧ Very water-soluble, not metabolized, renally excreted.
Sugammadex (Bridion®)
➧ Sugammadex is a modified γ-cyclodextrin, with a lipophilic core and a hydrophilic periphery.
➧ A selective relaxant binding agent that encapsulates and forms high-affinity complexes with steroidal neuromuscular blocking agents; rocuronium, vecuronium, and to a lesser extent pancuronium, preventing their action that will enable anesthesiologists to rapidly reverse shallow and profound neuromuscular block induced by them.
➧ The +ve charge of ammonium groups of rocuronium or vecuronium are attracted to the -ve charged sugar group in the center of the ring.
➧ Sugammadex is inactive against non-steroidal neuromuscular blocking agents, like succinylcholine and cisatracurium.
Advantages:
1- Can provide immediate reversal when required.
2- Provides complete and rapid reversal of profound neuromuscular blockade.
3- Minimizes the risk of residual postoperative paralysis.
Uses:
➧ Sugammadex is indicated in adults for:
1- Routine reversal of shallow and profound neuromuscular blockade induced by rocuronium or vecuronium.
2- Immediate reversal of neuromuscular blockade at 3 min. after administration of rocuronium.
3- In combination with rocuronium, may provide an alternative to succinylcholine.
4- Avoids the need to use acetylcholinesterase inhibitors (AChEIs) (neostigmine) and muscarinic antagonists (atropine/ glycopyrrolate) and elimination of side effects associated with them and the mechanical mixing of two drugs.
5- Sugammadex has no potential to cause drug-drug interaction (=DDI) due to inhibition or induction of drug-metabolizing enzymes.
Pharmacokinetics:
• Volume of distribution: ≈ 12-15 L
• Plasma half-life: ≈ 2.2 h
• Clearance: ≈ 91 mL/min (≈ GFR)
• Blood-brain barrier penetration (< 3% in rats)
• Placental transfer (< 2-6% in rats and rabbits)
• Low plasma protein binding, No metabolism
• Sugammadex-Rocuronium complex is almost renally excreted
Dosing Recommendations:
Routine Reversal:
➧ A dose of 2 mg/kg is only recommended if spontaneous recovery has occurred up to the reappearance of T2 (shallow blockade) following rocuronium or vecuronium-induced blockade.
➧ A dose of 4 mg/kg is recommended if recovery has reached 1-2 post-tetanic counts (PTC) (profound blockade) following rocuronium or vecuronium-induced blockade.
Immediate Reversal:
➧ A dose of 16 mg/kg is recommended for 3 min. following the administration of rocuronium.
There are no data to support the use of sugammadex for immediate reversal following the vecuronium-induced blockade.
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