MEASURED CONTEXT-SENSITIVE HALF-TIMES OF REMIFENTANIL AND ALFENTANIL
MEASURED CONTEXT-SENSITIVE HALF-TIMES OF REMIFENTANIL AND ALFENTANIL
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DOI：
10.1097/00000542-199511000-00009
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发表时间：
1995-11-01
期刊：
影响因子：
8.8
通讯作者：
SMITH, RL
中科院分区：
文献类型：
--
作者：
KAPILA, A;GLASS, PSA;SMITH, RL
背景：上下文相关的半衰期，而不是终末消除半衰期，已被认为是一种更具临床相关性的措施，用于在给定持续时间内持续输注后降低药物浓度。上下文相关的半衰期是从使用已知药代动力学参数的计算机建模得出的。模拟的阿芬太尼输注3小时的上下文相关半衰期为50-55分钟，瑞芬太尼为3分钟，最终消除半衰期阿尔芬太尼为111分钟，瑞芬太尼为12-30分钟。模拟的上下文相关半衰期是否反映了药物浓度或药效下降50%的真实时间尚未得到检验。方法：30名志愿者接受同等有效浓度的瑞芬太尼或阿芬太尼3h的输注。以每分钟通气量降至7.5%ET(CO2)作为药物疗效的指标。在药物输注过程中和药物输注后，测量每分钟的换气反应，并采集血药浓度样本。结果：瑞芬太尼输注3h后的药动学上下文敏感半衰期为3.2±0.9min，药效偏移量为5.4±1.8min。阿芬太尼的药代动力学背景相关半衰期为47.3±12min，药效偏移量为54.0±/-48min。由受试者模拟的瑞芬太尼和阿芬太尼的终末消除半衰期分别为11.8+/-5.1分钟和76.5+/-12.6分钟。结论实验测得的上下文相关半衰期与先前所建的上下文相关半衰期非常接近。这项研究的结果证实了与终末消除半衰期相比，上下文相关的半衰期在描述药物抵销方面的价值。
Background: The context-sensitive half-time, rather than the terminal elimination half-life, has been proposed as a more clinically relevant measure of decreasing drug concentration after a constant infusion of a given duration. The context-sensitive half-time is derived from computer modelling using known pharmacokinetic parameters. The modelled context-sensitive half-time for a 3-h infusion of alfentanil is 50-55 min and is 3 min for remifentanil, The terminal elimination half-life is 111 min for alfentanil and 12-30 min for remifentanil. It has not been tested whether the modelled context-sensitive half-time reflects the true time for a 50% decrease in drug concentration or drug effect.Methods: Thirty volunteers received a 3-h infusion of remifentanil or alfentanil at equieffective concentrations. Depression of minute ventilation to 7.5% ET(CO2) was used as a measure of drug effect. Minute ventilation response was measured, and blood samples for drug concentration were taken during and after drug infusion. The recovery of minute ventilation (drug effect) and decrease in blood drug concentration was plotted, and the time for a 50% change was determined,Results: The measured pharmacokinetic context-sensitive half-time for remifentanil after a 3-h Infusion was 3.2 +/- 0.9 min, and its pharmacodynamic offset was 5.4 +/- 1.8 min. Alfentanil's measured pharmacokinetic context-sensitive half-time was 47.3 +/- 12 min, and its pharmacodynamic offset was 54.0 +/- 48 min. The terminal elimination half-life modelled from the volunteers was 11.8 +/- 5.1 min for remifentanil and 76.5 +/- 12.6 min for alfentanil.Conclusions The measured context-sensitive half-times were in close agreement with the context-sensitive half-times previously modelled for these drugs. The results of this study confirm the value of the context-sensitive half-time in describing drug offset compared to the terminal elimination half-life.