Moffat A C, Osborne G A, Badcock N R, Maranucci P, Nyman T, Russell W J
Department of Anaesthesia & Intensive Care, Royal Adelaide Hospital, South Australia.
Anaesthesia. 1995 Jan;50(1):3-8. doi: 10.1111/j.1365-2044.1995.tb04503.x.
The clinical pharmacodynamics of temazepam were investigated in patients who received spinal anaesthesia. Total plasma and cerebrospinal fluid temazepam concentrations were measured and correlated with the clinical effects. Sedation was measured by three separate methods. None, including an aggregated score of all three measures, was correlated closely with either the plasma or the cerebrospinal fluid levels (p = 0.86 and 0.12 respectively). Anxiety was measured before and after premedication. The two scores were correlated but the change in anxiety after premedication did not correlate with either the plasma or the cerebrospinal fluid concentrations (p = 0.11 and 0.45 respectively). Short-term memory was measured before and after premedication. The decline in short-term memory ability was moderately well correlated with both the plasma and the cerebrospinal fluid levels (p = 0.0005 and 0.013 respectively). With temazepam, the variation in sedative and anxiolytic effects between subjects is explained not by differences in pharmacokinetics but rather by differences in the pharmacodynamic response. Because sedative and anxiolytic effects are poorly correlated, but the amnesic effect is well correlated with temazepam concentrations, different sites of action for these effects are suggested.
在接受脊髓麻醉的患者中研究了替马西泮的临床药效学。测量了血浆和脑脊液中替马西泮的总浓度，并将其与临床效果进行关联。通过三种不同方法测量镇静作用。包括所有三项测量的综合评分在内，均与血浆或脑脊液水平无密切关联（分别为p = 0.86和0.12）。在术前用药前后测量焦虑水平。两项评分相关，但术前用药后焦虑水平的变化与血浆或脑脊液浓度均无关联（分别为p = 0.11和0.45）。在术前用药前后测量短期记忆。短期记忆能力的下降与血浆和脑脊液水平均有中度良好的相关性（分别为p = 0.0005和0.013）。对于替马西泮，受试者之间镇静和抗焦虑作用的差异不是由药代动力学差异解释，而是由药效学反应差异解释。由于镇静和抗焦虑作用相关性较差，但遗忘作用与替马西泮浓度相关性良好，提示这些作用有不同的作用位点。
