脑外科病人丙泊酚的群体药效动力学

李玉红;徐建红;芮建中;徐建国

中国药学杂志 ›› 2006, Vol. 41 ›› Issue (17) : 1334-1337.

中国药学杂志 ›› 2006, Vol. 41 ›› Issue (17) : 1334-1337.
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脑外科病人丙泊酚的群体药效动力学

  • 李玉红;徐建红;芮建中;徐建国
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Population Pharmacodynamics of Propofol in Neurosurgical Patients

  • LI Yu-hong1,XU Jian-hong1,RUI Jian-zhong2,XU Jian-guo3
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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;Sigmoid Emax模型的药效参数Emax,EC50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,r2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Sigmoid Emax模型描述丙泊酚的药效动力学特征。

Abstract

OBJECTIVE To analyze population pharmacodynamics of propofol in neurosurgical patients and to discuss the influences of the age, weight or gender on the propofol pharmacodynamics. METHODS Twenty-seven ASA Ⅰ~Ⅱ elective neurosurgical patients were treated with propofol 2 mg·kg-1 for 5 min and maintained the infusion of propofol 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 propofol 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(r2 were 0.911 2, 0.9146, and 0.926, respectively). CONCLUSION Linear additive, linear exponential and Sigmoid Emax models can describe the pharmacodynamics of propofol.

关键词

丙泊酚 / 群体药效动力学 / 双频谱脑电图指数

Key words

propofol / population pharmacodynamics / bispectral index

引用本文

导出引用
李玉红;徐建红;芮建中;徐建国. 脑外科病人丙泊酚的群体药效动力学[J]. 中国药学杂志, 2006, 41(17): 1334-1337
LI Yu-hong;XU Jin-hong;RUI Jin-zhong;XU Jin-guo. Population Pharmacodynamics of Propofol in Neurosurgical Patients [J]. Chinese Pharmaceutical Journal, 2006, 41(17): 1334-1337

参考文献

[1] GLASS P S,BLOOM M,KEARSE L,et al. Bispectral analysis measurement sedation and memory effects of propofol,midazolam,isoflurane,and alfentanil in healthy volunteers[J] .Anesthesiology,1997,86:836-847. [2] LUO A L,YI J,GUO X Y,et al. Concentration of propofol in cerebral spinal fluid: target-controlled infusion[J] .Chin Med J,2004,117: 231-234. [3] ZHANG M Z,WANG S J,HANG Y N. Comparison between the performance of bispectral index and auditory evoked potential index to predict the level of consciousness during propofol sedation with target controlled infusion[J] .Chin J Anesthesiol,2002,22(3): 136-139. [4] KEARSE L A,ROSOW C,ZESLAVSKY A,et al. Bispectral analysis of electroencephalogram predicts conscious processing of information during propofol sedation and hypnosis[J] .Anaesthesiology,1998,88: 25-34. [5] MALINGA M,PEITFLAUX F,LEPAGE J Y,et al. Dose-response relationship between target-controlled concentration of propofol and bispectral index[J] .Br J Anaesth,1998,80(suppl): A132. [6] PLUMMER G F. Improved method for the determination of propofol in blood by high-performance liquid chromatography with fluorescence detection [J] .J Chromatogr,1987,421:171-176. [7] LIN S S,CAI W M,RUI J Z. The New Theory and New Method for Therapeutic Drug Monitoring[M] . Beijing: Publishing House of Chinese Medicine,2002:106-133. [8] SCHNIDER T W,MINTO C F,SHAFER S L,et al. The influence of age on propofol pharmacodynamics[J] .Aneaesthesiology,1999,90: 1502-1516. [9] ARDEN J R,HOLLEY F O,STANSKI D R. Increased sensitivity to etomidate in the elderly: initial distribution versus altered brain response[J] .Aneaesthesiology,1986,65: 19-27. [10] JACOBS J R,REVES J G,MARTY J,et al. Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam[J] .Anesth Analg,1995,80: 143-148. [11] MINTO C F,SCHNIDER T W,EGAN T D,et al. Influence of age and gender on the pharmacokinetics and phmacodynamics of remifentanil. I. Model development[J] .Aneaesthesiology,1997,86: 10-23. [12] SHEINER L B,DONALD R,STANSKI M D,et al. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurine[J] .Clin Pharmacol Ther,1979,25: 358. [13] ENGDAHL O,ABRAHAMS M,BJORNSSON A,et al. Cerebrospinal fluid concentration of propofol during anaesthesia in humans[J] .Br J Anaesth,1998,81: 957-959.

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