脑外科病人丙泊酚的群体药效动力学  

Population Pharmacodynamics of Propofol in Neurosurgical Patients

作　　者：李玉红[1] 徐建红[1] 芮建中[2] 徐建国[3] 

机构地区：[1]浙江大学医学院第一附属医院麻醉科,杭州310003 [2]南京军区总医院临床药理学研究所,南京210002 [3]南京金陵医院麻醉科,南京210002

出　　处：《中国药学杂志》2006年第17期1334-1337,共4页Chinese Pharmaceutical Journal

摘　　要：目的 考察脑外科病人丙泊酚的群体药效动力学特征，以及年龄、体重或性别等固定效应对丙泊酚药效动力学的影响。方法 27例ASAⅠ～Ⅱ级择期脑外科手术病人。经静脉注射丙泊酚2mg·kg^-1（5min），再以10mg·kg^-1·h^-1速率微量泵维持5min，之后停用丙泊酚。分别于给药前，给药后不同时间根据BIS index值的变化抽取血液和脑脊液，每个病人抽取6个标本。用高效液相色谱荧光法检测血浆中和脑脊液中的丙泊酚浓度；选择双频谱脑电图指数（bispectral index，BIS index）作为药效指标。首先用Excel对数据进行预处理，再用NONMEM法对效应BIS index值与血浆和与脑脊液丙泊酚浓度分别进行模型拟合．并考察年龄、体重或性别等固定效应对丙泊酚药效动力学的影响。结果 NONMEM程序分析的结果：线性加法模型的药效参数a，b分别为1．11和95．4；线性指数模型的药效参数a，b分别为1．05和92．7；Sitgnoid Emax模型的药效参数Emax,EG50和N分别为119，53．6和1．51。用上述3种模型参数预算脑脊液的丙泊酚浓度与实测浓度的相关性很好，r^2值分别为0．9112．0．9146，0．926。结论 可用线性加法模型、线性指数模型和Sitgnoid Emax模型描述丙泊酚的药效动力学特征。OBJECTIVE To analyze population pharmacodynamics of propofol in neurosurgical patients and to discuss the influences of the age, weight or gender on the pmpofol pharmacodynamics. METHODS Twenty-seven ASA Ⅰ-Ⅱ elective neurosurgical patients were treated with pmpofol 2 mg·kg^-1 for5 min and maintained the infusion of pmpofol 10 mg·kg^-1·h^-1 for 5 min. CSF and arterial blood were collected simultaneously before infusion and at different time points after infusion. The concentrations of pmpofol were measured with HPLC with fluorescence detection. At the same time of sample collection, BIS index（BIS） was recorded. Model simulation was performed and the influences of age, weight, and gender were investigated by using NONMEM program. RESULTS The parameters of a and b for linear addictive model were 1.11 and 95.4; the parameters of a and b for linear exponential model were 1.05 and 92.7; the parameters of Emax, EC50 and N for Sigmoid Emax model were 119,53.6 and 1.51, respectively. The predicted concentrations of CSF showed a good correlation with the measured concentrations（ r^2 were 0.911 2, 0.9146, and 0.926, respectively）. CONCLUSION Linear additive, linear exponential and Sigmoid Emax models can describe the pharmacodynamics of pmpofol.

关 键 词：丙泊酚 群体药效动力学 双频谱脑电图指数 

分 类 号：R969[医药卫生—药理学]