瑞芬太尼在人体中的代谢动力学研究

建立了用液相色谱-串联质谱技术进行瑞芬太尼代谢动力学研究的方法。比较了不同停药时间对瑞芬太尼浓度及代谢产物的影响。瑞芬太尼浓度测定采用串联质谱的选择反应监测技术,以m/z377>345为定量离子对,定量检出限为0.5μg/L。代谢产物的测定采用液质联用技术,同时测定二级质谱。在停药8min后,瑞芬太尼代谢90%。氧化和水解是瑞芬太尼的主要代谢反应,瑞芬太尼在人体中形成4种代谢物。该研究方法简单、快速、灵敏,具有广泛的应用性。     

高剂量瑞芬太尼对冠心病无痛胃镜检查患者循环系统及cTnI、BNP的影响

本文旨在探讨高剂量瑞芬太尼对冠心病无痛胃镜检查患者循环系统及心肌损伤的影响。无痛胃镜检查的冠心病患者96例随机分为LR组(丙泊酚+瑞芬太尼0.2μg·kg^-1,n=48)和HR组(丙泊酚+瑞芬太尼0.5μg·kg^-1,n=48)。比较2组睫毛反射消失时间、胃镜检查时间、苏醒时间及丙泊酚用量,观察检查前(T 0)、检查开始即刻(T 1)、检查开始后5 min(T 2)、10 min(T 3)、检查结束即刻(T 4)SBP、HR、RPP及ST段、T波变化,并检测2组胃镜检查前和结束时cTnI、BNP等指标。结果显示,HR组睫毛反射消失时间、胃镜检查时间、丙泊酚用量低于LR组(P<0.05);T 3、T 4时HR组SBP、HR及RPP低于LR组(P<0.05);HR组T1、T2时ST段与T波改善情况优于LR组(P<0.05);HR组检查后cTnI、BNP水平低于LR组(P<0.05);HR组术中一般体动反应发生率低于LR组(P<0.05)。表明0.5μg·kg^-1瑞芬太尼复合丙泊酚用于冠心病无痛胃镜检查麻醉效果满意,对患者循环系统及cTnI、BNP的影响较小。     

Simultaneous determination of propofol and remifentanil in rat plasma by liquid chromatography–tandem mass spectrometry: application to preclinical pharmacokinetic drug–drug interaction analysis

Propofol (Pro) is an ultra‐short‐acting hypnotic agent used for general anesthesia that has no analgesic properties. Remifentanil (Rem) is an ultra‐short‐acting opioid administered concomitantly as an analgesic with Pro. To evaluate the pharmacokinetic interactions between Pro and Rem, we developed and validated a method combining high‐performance liquid chromatography with tandem mass spectrometry for simultaneous determination of Pro and Rem. The proposed method was successfully used to study the pharmacokinetic interactions of Pro and Rem coadministered to rats. Copyright © 2014 John Wiley & Sons, Ltd.     

Parameter optimization of pharmacokinetics based on artificial immune network

A new method for parameter optimization of pharmacokinetics based on an artificial immune network named PKAIN is proposed. To improve local searching ability of the artificial immune network, a partition-based concurrent simplex mutation is developed. By means of evolution of network cells in the PKAIN artificial immune network, an optimal set of parameters of a given pharmacokinetic model is obtained. The Laplace transform is applied to the pharmacokinetic differential equations of remifentanil and its major metabolite, remifentanil acid. The PKAIN method is used to optimize parameters of the derived compartment models. Experimental results show that the twocompartment model is sufficient for the pharmacokinetic study of remifentanil acid for patients with mild degree of renal impairment.