title: Administration to humans of ORG 21465, a water soluble steroid i.v. anaesthetic agent.
abstract: Ten male volunteers received a 1-min i.v. infusion of a new water soluble steroid anaesthetic agent, ORG 21465. Individuals received doses ranging 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 became 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 analysis supported a three-compartment (non-weight-related) model with compartmental volumes V1, V2 and V3 of 4.31, 14.2 and 89.4 litre, respectively. Clearance from the central compartment V1 was 1.55 litre min-1. Inter-compartmental clearances Q1 and Q2 were 2.54 and 1.79 litre min-1. We found that ORG 21465 was an effective anaesthetic in humans. The relationship between sedation, anaesthesia and excitation requires further exploration.
authors.affiliation: Department of Anaesthesia, Derriford Hospital, Plymouth, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Sneyd
authors.forename: P M
authors.initials: PM
authors.lastname: Wright
authors.forename: M
authors.initials: M
authors.lastname: Cross
authors.forename: P
authors.initials: P
authors.lastname: Thompson
authors.forename: G
authors.initials: G
authors.lastname: Voortman
authors.forename: M M
authors.initials: MM
authors.lastname: Weideman
authors.forename: C J
authors.initials: CJ
authors.lastname: Andrews
authors.forename: C J
authors.initials: CJ
authors.lastname: Daniell
mesh_terms: D000328:Adult; D000771:Anesthesia, Intravenous / Q000379:methods; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D011277:Pregnanediones / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D014867:Water
chemical_list: D018686:Anesthetics, Intravenous; C109272:ORG 21465; D011277:Pregnanediones; D014867:Water