ADMINISTRATION TO HUMANS OF ORG-21465, A WATER-SOLUBLE STEROID IV ANESTHETIC AGENT

Ten male volunteers received a 1-min i.v. infusion of a new water solu ble steroid anaesthetic agent, ORG 21465. Individuals received doses r anging from 0.8 to 1.8 mg kg(-1). All subjects experienced venous pain at the site of injection; those receiving 1.0 mg kg(-1) or more becam e anaesthetized, There was no evidence of histamine release and apnoea did not occur. Excitatory phenomena were observed in all subjects and were dose related; no spikes were seen on the EEG. Pharmacokinetic an alysis supported a three-compartment (non-weight-related) model with c ompartmental volumes V-1, V-2 and V-3 of 4.31, 14.2 and 89.4 litre, re spectively. Clearance from the central compartment V-1 was 1.55 litre min(-1). Inter-compartmental clearances (Q) over dot(1) and (Q) over d ot(2) Were 2.54 and 1.79 litre min(-1). We found that ORG 21465 was an effective anaesthetic in humans. The relationship between sedation, a naesthesia and excitation requires further exploration.