一种用于预测苯二氮䓬类药物药理活性的起效时间和持续时间的药代动力学/药效学/受体结合模型。

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

作者信息

Jack M L, Colburn W A, Spirt N M, Bautz G, Zanko M, Horst W D, O'Brien R A

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 1983;7(4-6):629-35. doi: 10.1016/0278-5846(83)90036-2.

Abstract

Ex vivo receptor binding as a function of time was determined in Charles River rats. 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. The model was subsequently used to predict changes in receptor binding and pharmacodynamics as a function of changes in pharmacokinetics. 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.

摘要

在查尔斯河大鼠中测定了离体受体结合随时间的变化情况。利用三种苯二氮䓬类诱导剂（地西泮、劳拉西泮和咪达唑仑）在人体中的药代动力学和蛋白结合参数以及在大鼠脑中的离体受体结合参数，建立并测试了一个药代动力学/药效学/受体结合模型。随后，该模型被用于预测受体结合和药效学随药代动力学变化的情况。结果发现，该模型能够很好地预测正常受试者以及在某些病理生理状况和某些药物相互作用情况下镇静和失忆特性的相对起效时间和持续时间。