First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial

BMC Anesthesiology

Research Article

Ann E Rigby-Jones¹  J Robert Sneyd¹  Peter Vijn²  Patrick Boen²  Maurice Cross³ 

[1] Peninsula College of Medicine & Dentistry, University of Plymouth, The John Bull Building, Research Way, PL6 8BU, Tamar Science Park, Plymouth, UK;Schering-Plough Corporation, 56 Livingston Ave, 07068, Roseland, NJ, USA;Veeda Clinical Research, 119 Looseleigh Lane, PL6 5HH, Derriford Plymouth, UK;

关键词: Pharmacokinetic Model;    Target Concentration;    Short Infusion;    Intravenous Anaesthetic;    Target Control Infusion;   

DOI  :  10.1186/1471-2253-10-10

 received in 2009-11-06, accepted in 2010-06-29,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundOrg 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data.MethodsIn the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg.ResultsWithin the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter.ConclusionsOrg 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics.

【 授权许可】

Unknown   
© Rigby-Jones et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.