A population analysis of the pharmacokinetics and pharmacodynamics of midazolam in the rat

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Abstract
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 (¯xs 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.