A New Agent to Reverse Rocuronium?

  1. For those of you interested the development of new methods to antagonize neuromuscular blockade, I've posted the abstract concerning human use of Org. 25969. Enjoy!

    Anesthesiology. 2005 Oct;103(4):695-703.

    First Human Exposure of Org 25969, a Novel Agent to Reverse the Action of Rocuronium Bromide.

    Gijsenbergh F, Ramael S, Houwing N, van Iersel T.

    BACKGROUND:: Acetylcholinesterase inhibitors are widely used for the reversal of neuromuscular blocking agents. However, acetylcholinesterase inhibitors have several side effects and are not effective during profound block. Org 25969 is a modified gamma-cyclodextrin that encapsulates the neuromuscular blocking agent, rocuronium bromide (Esmeron(R)/Zemuron(R), NV Organon, Oss, The Netherlands), forming a tightly bound complex with an association constant of approximately 10 m. Chemical encapsulation of rocuronium promotes dissociation of rocuronium from the acetylcholine receptor, thereby reversing the neuromuscular block without the side effects associated with acetylcholinesterase inhibitors. METHODS:: Twenty-nine healthy male volunteers were enrolled to investigate the safety, pharmacokinetics, and efficacy of Org 25969. In part 1, Org 25969 or placebo was administered to 19 subjects during one to three treatment periods each. In part 2, a further 10 subjects received general anesthesia on two separate occasions, using an intubating dose of 0.6 mg/kg rocuronium. Three minutes after rocuronium administration, Org 25969 or placebo was given in random order. Six doses of 0.1-8.0 mg/kg Org 25969 were evaluated. Neuromuscular block was measured using an acceleromyograph, the TOF-Watch-SX(R) (NV Organon, Oss, The Netherlands). RESULTS:: All adverse events related to Org 25969 treatment were of limited duration and mild intensity, except for a period of paresthesia, seen in one patient receiving 8 mg/kg Org 25969, which was of moderate intensity. No adverse events required any treatment, and all subjects recovered from them. When 8 mg/kg Org 25969 was given, the train-of-four ratio returned to 0.9 within 2 min after its administration. No signs of recurarization were observed. CONCLUSIONS:: Org 25969 was both well tolerated and effective in reversing neuromuscular block induced by rocuronium in 29 human volunteers.
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  2. 6 Comments

  3. by   preCRNA
    Quote from charles-thor
    For those of you interested the development of new methods to antagonize neuromuscular blockade, I've posted the abstract concerning human use of Org. 25969. Enjoy!

    Anesthesiology. 2005 Oct;103(4):695-703.

    First Human Exposure of Org 25969, a Novel Agent to Reverse the Action of Rocuronium Bromide.

    Gijsenbergh F, Ramael S, Houwing N, van Iersel T.

    BACKGROUND:: Acetylcholinesterase inhibitors are widely used for the reversal of neuromuscular blocking agents. However, acetylcholinesterase inhibitors have several side effects and are not effective during profound block. Org 25969 is a modified gamma-cyclodextrin that encapsulates the neuromuscular blocking agent, rocuronium bromide (Esmeron(R)/Zemuron(R), NV Organon, Oss, The Netherlands), forming a tightly bound complex with an association constant of approximately 10 m. Chemical encapsulation of rocuronium promotes dissociation of rocuronium from the acetylcholine receptor, thereby reversing the neuromuscular block without the side effects associated with acetylcholinesterase inhibitors. METHODS:: Twenty-nine healthy male volunteers were enrolled to investigate the safety, pharmacokinetics, and efficacy of Org 25969. In part 1, Org 25969 or placebo was administered to 19 subjects during one to three treatment periods each. In part 2, a further 10 subjects received general anesthesia on two separate occasions, using an intubating dose of 0.6 mg/kg rocuronium. Three minutes after rocuronium administration, Org 25969 or placebo was given in random order. Six doses of 0.1-8.0 mg/kg Org 25969 were evaluated. Neuromuscular block was measured using an acceleromyograph, the TOF-Watch-SX(R) (NV Organon, Oss, The Netherlands). RESULTS:: All adverse events related to Org 25969 treatment were of limited duration and mild intensity, except for a period of paresthesia, seen in one patient receiving 8 mg/kg Org 25969, which was of moderate intensity. No adverse events required any treatment, and all subjects recovered from them. When 8 mg/kg Org 25969 was given, the train-of-four ratio returned to 0.9 within 2 min after its administration. No signs of recurarization were observed. CONCLUSIONS:: Org 25969 was both well tolerated and effective in reversing neuromuscular block induced by rocuronium in 29 human volunteers.
    That is awesome. I hope that this drug continues to have good results because it would make those shorter cases a little more managable.

    preCRNA
  4. by   miloisstinky
    Does anyone think this would make sux obsolete?
  5. by   preCRNA
    Quote from miloisstinky
    Does anyone think this would make sux obsolete?
    I think that it may. You could have a fast onset like succs then a fast reversal without the negative side effects like fasciculations and Type II block, that is assuming that you would be able to reverse the block that easily. I would be great for intubations especially.

    preCRNA
  6. by   charles-thor
    Does anyone think this would make sux obsolete?

    I'd imagine that this stuff is going to be quite expensive, so I wouldn't count on sux going anywhere anytime soon.
  7. by   miloisstinky
    i hope your right, cause i LOVE sux. i already see myself as that oldtimer crna that used to use a drug called succinylcholine......gonna be hard to let go it think
  8. by   zrmorgan
    Quote from miloisstinky
    Does anyone think this would make sux obsolete?
    I dont know about making sux obsolete, but the prospect of making AChEIs obsolete, as well as not having to give antimuscarinics is very encouraging. Keep a close eye on organon's parent corporation traded on the NASDAQ: http://finance.yahoo.com/q?s=AKZOY, especially as this drug becomes more available to us in practice.

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