title: Pharmacodynamics and pharmacokinetics of an infusion of Org 9487, a new short-acting steroidal neuromuscular blocking agent.
abstract: 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.
authors.affiliation: Research Group for Experimental Anesthesiology and Clinical Pharmacology, University Hospital, Groningen, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: van den Broek
authors.forename: J M
authors.initials: JM
authors.lastname: Wierda
authors.forename: N J
authors.initials: NJ
authors.lastname: Smeulers
authors.forename: J H
authors.initials: JH
authors.lastname: Proost
mesh_terms: D000293:Adolescent; D000328:Adult; D000768:Anesthesia, General; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009469:Neuromuscular Junction / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013997:Time Factors; D014673:Vecuronium Bromide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
chemical_list: D003473:Neuromuscular Nondepolarizing Agents; D014673:Vecuronium Bromide; C082938:rapacuronium