七氟烷与瑞芬太尼在抑制强直电刺激中的药效学相互作用  

Pharmacodynamic interaction between sevoflurane and remifentanil regarding tolerance of responses to electrical tetanus stimuli

作　　者：王慧玲[1] 杨璐[1] 张利萍[1] 郭向阳[1] 毕姗姗[2] 卢炜[2] 

机构地区：[1]北京大学第三医院麻醉科,北京100191 [2]北京大学药学院,北京100191

出　　处：《中国新药杂志》2012年第9期1020-1025,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30801423)

摘　　要：目的:应用响应曲面分析法,研究瑞芬太尼(≤10 ng·mL-1)与七氟烷(≤3.4%)在抑制强直电刺激(ETS)引起的体动和循环反应中的药效学相互作用。方法:选择ASAΙ级、年龄20～50岁手术患者65例,随机选定呼气末七氟烷浓度(0%～3.4%),瑞芬太尼采用靶控输注方式。所有患者呼气末七氟烷浓度维持恒定,瑞芬太尼的靶控输注浓度逐渐由0 ng.mL-1增加至10 ng.mL-1。分别在呼气末七氟烷浓度和瑞芬太尼血浆浓度与效应室浓度达到平衡后,观察患者对ETS引起的体动反应和循环反应。应用响应曲面模型分析七氟烷与瑞芬太尼在抑制ETS中的药效学相互作用;应用NONMEM软件分析拟合药效反应的模型参数;应用Minitab软件绘制三维响应曲面图。结果:瑞芬太尼与七氟烷相互作用的三维响应曲面表明,二者在抑制ETS引起的体动反应和循环反应时具有明显的协同作用。3 ng·mL-1的瑞芬太尼使七氟烷抑制ETS的MAC值降低了50%以上,此后瑞芬太尼在降低七氟烷抑制ETS引起的体动和循环反应的MAC值上表现出封顶效应。瑞芬太尼10 ng·mL-1时,抑制ETS体动和循环反应的七氟烷的MAC值分别为0.41%和0.47%。结论:响应曲面分析法可以定性和定量的分析瑞芬太尼与七氟烷的药效学相互作用规律。在临床应用浓度范围内,瑞芬太尼与七氟烷在抑制ETS的体动反应和循环反应上,表现出明显的协同作用,瑞芬太尼与七氟烷在抑制ETS引起的循环反应方面的协同作用大于抑制体动反应的协同作用。Objective：To describe the pharmacodynamic interactions between remifentanil（≤10ng·mL-1）and sevoflurane（≤3.4%） in suppressing somatic and hemodynamic responses to electrical tetanus stimuli（ETS） with response surface method.Methods：Sixty-five patients of ASAⅠ,aged 20～50 years,were scheduled for study.Each patient was randomly assigned to one of sevoflurane concentrations（0%～3.4%）.Remifentanil was administrated by TCI.Each patient received a fixed end-tidal concentration of sevoflurane.The target concentrations of remifentanil were increased in a stepwise ascending fashion from 0ng·mL-1 to 10ng·mL-1.After reaching pseudo-steady state drug levels,the somatic and hymodynamic responses to ETS were assessed at each target concentration pair.The pharmacodynamic interactions between remifentanil and sevoflurane were analyzed by response surface method.NONMEM was used to estimate the parameter values.Minitab software was used to construct the three-dimensional response surfaces.Results：The three-dimensional response surfaces showed that sevoflurane-remifentanil interactions were strongly synergistic for blunting responses to ETS.When the target concentration of remifentanil was 3ng·mL-1,the MAC of sevoflurane for blunting responses to ETS decreased by more than 50%.Then ceiling effect was seen when the target concentration of remifentanil was further increased.When the target concentration of remifentanil was 10ng·mL-1,the values of sevoflurane MAC for blunting somatic and hymodymamic responses to ETS were 0.41% and 0.47%,respectively.Conclusion：Response surface method can analyze the pharmacodynamic interactions between sevoflurane and remifentanil qualitatively and quantitatively.The interactions are strongly synergistic for blunting responses to ETS.Sevoflurane-remifentanil synergistic interactions on ablating hemodynamic responses to ETS are stronger than that on blunting somatic responses.

关 键 词：七氟烷 瑞芬太尼 强直电刺激 响应曲面 药物相互作用 

分 类 号：R971[医药卫生—药品]