Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non-depolarizing Neuromuscular-blocking Agents
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Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non-depolarizing Neuromuscular-blocking Agents. / Haerter, Friederike; Simons, Jeroen Cedric Peter; Foerster, Urs; Moreno Duarte, Ingrid; Diaz-Gil, Daniel; Ganapati, Shweta; Eikermann-Haerter, Katharina; Ayata, Cenk; Zhang, Ben; Blobner, Manfred; Isaacs, Lyle; Eikermann, Matthias.
In: ANESTHESIOLOGY, Vol. 123, No. 6, 12.2015, p. 1337-1349.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non-depolarizing Neuromuscular-blocking Agents
AU - Haerter, Friederike
AU - Simons, Jeroen Cedric Peter
AU - Foerster, Urs
AU - Moreno Duarte, Ingrid
AU - Diaz-Gil, Daniel
AU - Ganapati, Shweta
AU - Eikermann-Haerter, Katharina
AU - Ayata, Cenk
AU - Zhang, Ben
AU - Blobner, Manfred
AU - Isaacs, Lyle
AU - Eikermann, Matthias
PY - 2015/12
Y1 - 2015/12
N2 - 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 × 10 M and Ka = 3.8 × 10 M-). 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.
AB - 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 × 10 M and Ka = 3.8 × 10 M-). 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.
KW - Androstanols/antagonists & inhibitors
KW - Animals
KW - Atracurium/analogs & derivatives
KW - Dose-Response Relationship, Drug
KW - Heterocyclic Compounds, 4 or More Rings/pharmacology
KW - Male
KW - Neostigmine/pharmacology
KW - Neuromuscular Nondepolarizing Agents/antagonists & inhibitors
KW - Rats
KW - Rocuronium
KW - Sugammadex
KW - Sulfonic Acids/pharmacology
KW - Vecuronium Bromide/antagonists & inhibitors
KW - gamma-Cyclodextrins/pharmacology
U2 - 10.1097/ALN.0000000000000868
DO - 10.1097/ALN.0000000000000868
M3 - SCORING: Journal article
C2 - 26418697
VL - 123
SP - 1337
EP - 1349
JO - ANESTHESIOLOGY
JF - ANESTHESIOLOGY
SN - 0003-3022
IS - 6
ER -