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British Journal of Anaesthesia, 1994, Vol. 73, No. 3 331-335
© 1994 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

Pharmacodynamics and pharmacokinetics of an infusion of Org 9487, a new short-acting steroidal neuromuscular blocking agent

L. VAN DEN BROEK, MD, J. M. K. H. WIERDA, MD, PHD, N. J. SMEULERS, MD and J. H. PROOST, PHARMD, PHD

Research Group for Experimental Anesthesiology and Clinical Pharmacology, University Hospital Groningen, The Netherlands
Department of Pharmacology and Therapeutics, University Centre for Pharmacy Groningen, The Netherlands

Address for correspondence: Department of Anesthesiology, University Hospital, P.O. Box 30.001, 9700 RB Groningen, The Netherlands

We have evaluated in 10 anaesthetized patients the time course of action, infusion requirements, reversibility and pharmacokinetics of Org 9487. Org 9487 was administered as a bolus dose of 1.5 mg kg–1 followed by an infusion to maintain a block of 75–85% for 60 min. After recovery from the bolus dose, a mean dose of Org 9487 3.4 (SD 1.0) mg kg–1 h–1 was administered to maintain a mean neuromuscular block of 83 (3)%. During the final 15 min of infusion, the infusion requirements were 2.5 (1.1) mg kg–1 h–1 In the five patients who were allowed to recover spontaneously, a TOF ratio of 0.7 was reached 37.9 (12.4) min after stopping the infusion of Org 9487. In the five patients who received neostigmine, a TOF ratio of 0.7 was reached after 14.5 (6.1) min. Plasma clearance was 8.5 (30%) ml kg–1 min–1. Volume of distribution at steady state was 293 (55%) ml kg–1 Terminal half life and mean residence time were 71.7 (34%) and 33.4 (31%) min, respectively. The concentration of the 3-OH metabolite remained relatively low. Urinary excretion of Org 9487 and its metabolites was 22% in 24 h. In conclusion, a 1-h infusion of the short-acting drug Org 9487 changed its time course characteristics gradually from that of a short-acting neuromuscular blocking agent to that of a neuromuscular blocker with an intermediate duration of action.


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