Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits.
Pancuronium is a long-duration neuromuscular blocking drug (NMBD) that has been used in anesthetized rabbits at 0.1 mg/kg. However, there are limited data regarding the time course for recovery from this dose either spontaneously or with pharmacologic reversal. Here we defined the potency, onset, and recovery characteristics for the intermediate-duration NMBD cisatracurium and CW002 (a novel cysteine-inactivated molecule) in the rabbit, and test the hypothesis that these drugs may be alternatives to 0.1 mg/kg pancuronium for survival procedures. New Zealand white rabbits anesthetized with isoflurane were studied in a cross-over design. Potencies of cisatracurium and CW002 were defined as the effective dose for 95% depression of evoked muscle twitch (ED95). Responses to 3×ED95 were used to define onset (time to maximal effect), recovery index (RI; time from 25% to 75% recovery of twitch), and duration (time to complete recovery). Responses to all drugs were determined with and without reversal by neostigmine-glycopyrrolate or L-cysteine. CW002 was 4-fold more potent than was cisatracurium, but their onset, RI, and duration were similar. Pancuronium had similar onset and RI but longer duration, compared with cisatracurium and CW002. Reversal shortened the recovery index and duration for all 3 drugs. At 3×ED95, cisatracurium and CW002 had the same onset as did standard-dose pancuronium, but durations were shorter and more predictable. In addition, CW002 can be reversed without the potential side effects of cholinergic manipulation. We conclude that cisatracurium and CW002 are viable alternatives to pancuronium for survival studies in rabbits.
Tri-Institutional Training Program in Laboratory Animal Medicine and Science- Memorial Sloan-Kettering Cancer Center, The Rockefeller University, and Weill Cornell Medical College, New York, New York, USA; Comparative Bioscience Center, The Rockefeller University, New York, New York, USA. ldiaz@rockefeller.edu.
Leslie L
LL
Diaz
Departments of Anesthesiology and Pharmacology, Weill Cornell Medical College, New York, New York, USA.
Jingwei
J
Zhang
Departments of Anesthesiology and Pharmacology, Weill Cornell Medical College, New York, New York, USA.
Paul M
PM
Heerdt
D000818:Animals; D001279:Atracurium / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D006339:Heart Rate / Q000187:drug effects; D007530:Isoflurane / Q000008:administration & dosage; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010197:Pancuronium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits
C542547:CW 002; D007546:Isoquinolines; D009466:Neuromuscular Blocking Agents; D001279:Atracurium; D007530:Isoflurane; D010197:Pancuronium; C101584:cisatracurium