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Canadian Journal of Anesthesia, Vol 38, 430-435, Copyright © 1991 by Canadian Anesthesiologists' Society

ARTICLES

The pharmacodynamics and pharmacokinetics of Org 9426, a new non-depolarizing neuromuscular blocking agent, in patients anaesthetized with nitrous oxide, halothane and fentanyl

JM Wierda, UW Kleef, LM Lambalk, WD Kloppenburg and S Agoston
Research Group for Experimental Anesthesiology and Clinical Pharmacology, University of Groningen, The Netherlands.

The pharmacodynamics and pharmacokinetics of a new non-depolarizing neuromuscular blocking agent, Org 9426, were investigated. Ten patients undergoing elective head and neck surgery and anaesthetized with nitrous oxide, halothane and fentanyl, received a bolus dose of Org 9426 (1 mg.kg-1, 3 x ED90). The isometric contractions of the adductor pollicis muscle following ulnar nerve stimulation (0.1 Hz and intermittent TOF) were measured. Blood and urine were sampled over 8 and 24 hr, respectively. Concentrations of Org 9426 and its possible metabolites in plasma and urine were determined using HPLC. Pharmacokinetic variables were calculated by iterative linear least square regression analysis. Intubation conditions were excellent one minute after administration at a neuromuscular block of 88 (13)% (Mean (CV]. Onset time until maximum block, duration until 25% recovery of twitch height, and recovery from 25 until 75% of twitch height were 1.7 (32), 53 (19) and 20 (37) min, respectively. The TOF reached a ratio of 0.7 after 87 (19) min. Half lives were 1.8 (33), 19 (34), 131 (62) min, respectively, in a three exponential decay; distribution volume at steady-state and plasma clearance were 0.264 (56) L.kg-1 and 4.0 (21) ml.kg-1.min-1, respectively. Plasma concentration at 25% recovery of the twitch height was 1.0 mg.L-1. Within 24 h, 33 (37)% of Org 9426 was excreted unchanged in the urine. Metabolites were absent both in plasma and urine. We conclude that the difference in potency between Org 9426 and vecuronium is similar to the difference between their effective concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)


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Copyright © 1991 by the Canadian Anesthesiologists' Society.