Administration to humans of ORG 21465, a water soluble steroid i.v. anaesthetic agent |
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Authors: | Sneyd J R; Wright PMC; Cross M; Thompson P; Voortman G; Weideman M M; Andrews CJH; Daniell C J |
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Institution: | Department of Anaesthesia, Derriford Hospital, Derriford Road, Plymouth PL6 8DH UK |
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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.
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