PHARMACODYNAMICS AND PHARMACOKINETICS OF AN INFUSION OF ORG-9487, A NEW SHORT-ACTING STEROIDAL NEUROMUSCULAR BLOCKING-AGENT

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.