Peninsula College of Medicine & Dentistry, University of Plymouth, The John Bull Building, Research Way, Tamar Science Park, Plymouth PL6 8BU, UK.
BMC Anesthesiol. 2010 Jun 29;10:10. doi: 10.1186/1471-2253-10-10.
Org 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.
In 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.
Within 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.
Org 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.
Org 25435 是一种新型水溶性α-氨基酸酯静脉麻醉剂，在动物研究中表现令人满意。本研究旨在评估 Org 25435 的安全性、耐受性和疗效，并获得初步的药效学和药代动力学数据。
在短输注研究中，8 名健康男性志愿者接受了 1 分钟输注 0.25、0.5、1.0 或 2.0mg/kg（每组 2 名）；另外 10 名志愿者接受了 3.0mg/kg（n=5）或 4.0mg/kg（n=5）。初步药代动力学建模后，7 名受试者接受了 30 分钟滴定目标控制输注（TCI），总剂量为 5.8-20mg/kg。
在短输注研究中，所有志愿者在 3mg/kg 和 4mg/kg 时均成功麻醉。在 TCI 研究中，5 名受试者被麻醉，2 名受试者出现镇静迹象。Org 25435 在 2mg/kg 以上剂量时会导致低血压和心动过速。Org 25435 给药 30 分钟后麻醉恢复缓慢（13.7 分钟）。药代动力学模型表明，Org 25435 的上下文敏感半衰期略短于丙泊酚在 20 分钟内的输注时间，但此后逐渐延长。
Org 25435 在 1 分钟内以 3mg/kg 和 4mg/kg 的剂量静脉注射是一种有效的人类静脉麻醉剂。较长的输注可以维持麻醉，但恢复缓慢。麻醉期间出现低血压和心动过速以及停药后意识恢复缓慢表明，该化合物与目前可用的静脉麻醉剂相比没有优势。
