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[药物药代动力学中的种间异速生长比例关系]

[Interspecies allometric scaling in pharmacokinetics of drugs].

作者信息

Sylvia M

机构信息

Semmelweis Orvostudományi Egyetem, Gyógyszerészeti Intézet, Budapest.

出版信息

Acta Pharm Hung. 1998 Nov;68(6):350-4.

PMID:9987199
Abstract

Allometric scaling is an empirical examination of the relationships between the pharmacokinetic parameters and size (usually body weight, ratio of organ- and body weight, breathing number, etc.). Interspecies pharmacokinetics tend to approximate, the organism, as the sum of organs and tissues according to material balance. The allometric equations for the pharmacokinetic parameters were applied to scale the data with respect to pharmacokinetic time and remove the chronological time dependency. When the data of at least three species are available, the pharmacokinetic parameters can be fit according to body weight in log-log regression. Allometric scaling is not applicable in all cases, only when the selected species has similar physiological behaviour, such as protein-binding, metabolism, etc. Valuable information for the evaluation of the effect and the biopharmaceutical characteristics may emerge from more creative data analysis based on all result collected during the preclinical evaluation of a new drug. Author examined the applicability of the interspecies scaling method in the case of a new drug depogen, using drotaverin as reference. The pharmacokinetic data were collected from mouse, rat and dog and during the evaluation human data were applied too. The usual pharmacokinetic parameters were determined (MRT, MAT, beta, etc.), the results of allometric analysis were collected and the standard deviation of measured and calculated values were given.

摘要

异速生长比例缩放是对药代动力学参数与大小(通常是体重、器官与体重之比、呼吸频率等)之间关系的实证研究。种间药代动力学往往近似于将生物体视为根据物质平衡由器官和组织组成的总和。药代动力学参数的异速生长方程用于按药代动力学时间对数据进行缩放,并消除时间顺序依赖性。当至少有三个物种的数据可用时,药代动力学参数可以根据体重进行对数-对数回归拟合。异速生长比例缩放并非在所有情况下都适用,仅适用于所选物种具有相似生理行为的情况,如蛋白质结合、代谢等。基于新药临床前评估期间收集的所有结果进行更具创造性的数据分析,可能会得出有关评估疗效和生物制药特性的有价值信息。作者以屈他维林为参照,研究了种间比例缩放方法在新药德泊根情况下的适用性。从小鼠、大鼠和犬收集药代动力学数据,评估期间也应用了人类数据。测定了常用的药代动力学参数(平均滞留时间、平均吸收时间、β等),收集了异速生长分析的结果,并给出了测量值和计算值的标准差。

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