A pharmacokinetic/pharmacodynamic/receptor binding model to predict the onset and duration of pharmacological activity of the benzodiazepines期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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A pharmacokinetic/pharmacodynamic/receptor binding model to predict the onset and duration of pharmacological activity of the benzodiazepines

Authors:	ML Jack WA Colburn NM Spirt G Bautz M Zanko WD Horst RA O'Brien

Institution:	¹ Department of Pharmacokineties and Biopharmaceutics, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA ² Department of Pharmacology II, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA

Abstract:	1. 1. Ex vivo receptor binding as a function of time was determined in Charles River rats. 2. 2. The pharmacokinetic and protein binding parameters in man as well as the ex vivo receptor binding parameters in rat brain for three benzodiazepine induction agents, diazepam, lorazepam and midazolam, were used to develop and test a pharmacokinetic/ pharmacodynamic/receptor binding model. 3. 3. The model was subsequently used to predict changes in receptor binding and pharmaco-dynamics as a function of changes in pharmacokinetics. 4. 4. The model was found to be a good predictor of the relative onset and duration of the sedative and amnesic properties in normal subjects as well as in the presence of certain patho-physiological conditions and certain drug interactions. Author Keywords: relative receptor occupancy; pharmacokinetics; ex vivo binding

Keywords:	relative receptor occupancy pharmacokinetics ex vivo binding
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