Comparative effectiveness of calabadion and sugammadex to reverse non-depolarizing neuromuscular-blocking agents

Friederike Haerter, Jeroen Cedric Peter Simons, Urs Foerster, Ingrid Moreno Duarte, Daniel Diaz-Gil, Shweta Ganapati, Katharina Eikermann-Haerter, Cenk Ayata, Ben Zhang, Manfred Blobner, Lyle Isaacs, Matthias Eikermann

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Background: The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation. Methods: The dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose-response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine. Results: In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 109 M-1 and Ka = 3.8 × 107 M-1). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate. Conclusions: Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats.

Original languageEnglish (US)
Pages (from-to)1337-1349
Number of pages13
JournalAnesthesiology
Volume123
Issue number6
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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