Bienert Agnieszka, Wawrzyniak Katarzyna, Wiczling Paweł, Przybyłowski Krzysztof, Kokot Zenon J, Matysiak Jan, Pachutko Agnieszka, Józefowicz Martyna, Kusza Krzysztof, Grześkowiak Edmund
Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Marii Magdaleny 14, 61 - 861, Poznan, Poland.
Department of Anesthesiology and Intensive Therapy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, ul. Marii Skłodowskiej - Curie 9, 85-094, Bydgoszcz, Poland.
J Clin Pharmacol. 2015 Mar;55(3):307-16. doi: 10.1002/jcph.401. Epub 2014 Oct 1.
Recently oral melatonin has been proposed as an agent for premedication. In this study, we compared melatonin with clonidine, considering its anxiolytic properties as well as the influence of both agents on the pharmacokinetic, hypnotic, and hemodynamic effects of propofol during propofol-remifentanil total intravenous anesthesia (TIVA). The dataset under analysis included 32 patients scheduled for a functional endoscopic sinus surgery. The population pharmacokinetic modeling was done with NONMEM. The PK of propofol was described with a two-compartment disposition model, whereas the BIS and AAI were described with a sigmoidal Emax model linked with the propofol concentration via the biophase compartment. The anxiolytic effect was assessed by means of the visual analog scale for anxiety (VAS-A). The population PK/PD model was successfully developed to describe the data. No significant differences in the PK/PD of propofol were noted due to the premedication with clonidine and melatonin. Melatonin was less effective than clonidine in reducing patients' anxiety at the induction of anesthesia, whereas clonidine premedication was associated with greater decrease in heart rate and blood pressure. A decreased EC50 (2.47 vs. 3.17 mg/L) and increased slope (2.71 vs. 1.30) of the sigmoidal Emax relationship was observed for the AAI index, as compared with the BIS measurements.
最近，口服褪黑素已被提议作为一种术前用药。在本研究中，我们将褪黑素与可乐定进行了比较，考虑到其抗焦虑特性以及这两种药物在丙泊酚-瑞芬太尼全静脉麻醉（TIVA）期间对丙泊酚的药代动力学、催眠和血流动力学效应的影响。分析的数据集包括32例计划进行功能性鼻内镜鼻窦手术的患者。使用NONMEM进行群体药代动力学建模。丙泊酚的药代动力学用二室处置模型描述，而脑电双频指数（BIS）和听觉诱发电位指数（AAI）用通过生物相室与丙泊酚浓度相关联的S型Emax模型描述。通过焦虑视觉模拟量表（VAS-A）评估抗焦虑效果。成功建立了群体药代动力学/药效学（PK/PD）模型来描述数据。由于可乐定和褪黑素的术前用药，丙泊酚的PK/PD未观察到显著差异。在麻醉诱导时，褪黑素在减轻患者焦虑方面比可乐定效果差，而可乐定术前用药与心率和血压的更大降低有关。与BIS测量相比，AAI指数的S型Emax关系的半数有效浓度（EC50）降低（2.47对3.17mg/L）且斜率增加（2.71对1.30）。
