A POPULATION ANALYSIS OF THE PHARMACOKINETICS AND PHARMACODYNAMICS OF MIDAZOLAM IN THE RAT

被引:28
作者
AARONS, L [1 ]
MANDEMA, JW [1 ]
DANHOF, M [1 ]
机构
[1] LEIDEN UNIV,CTR BIOPHARMACEUT SCI,DIV PHARMACOL,2300 RA LEIDEN,NETHERLANDS
来源
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS | 1991年 / 19卷 / 05期
关键词
MIDAZOLAM; PHARMACOKINETIC-PHARMACODYNAMIC MODELING; EEG; POPULATION PHARMACOKINETICS; NONMEM;
D O I
10.1007/BF01062959
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The concentration-EEG effect relationship of midazolam in the rat was studied from a population perspective. Plasma concentration and EEG effect data from 27 rats were available for analysis. Effect parameters derived from aperiodic EEG analysis were used as effect parameters. The population analysis gave results that were similar to the sample theory estimates (xsBAR and SDs) obtained from the fits to individual data sets. Reanalysis of the EEG data using mean population pharmacokinetic parameters as input to the pharmacodynamic model led to poorer estimation of the pharmacodynamic parameters: particularly EC50. Inclusion of one observed plasma concentration per individual significantly improved the estimation of the pharmacodynamic parameters and led to results that were virtually indistinguishable from those obtained using complete pharmacokinetic data.
引用
收藏
页码:485 / 496
页数:12
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