外推法
分配量
配送量
体积热力学
缩放比例
异速滴定
消除速率常数
分布(数学)
药代动力学
统计
停留时间(流体动力学)
数学
化学
生物
医学
热力学
内科学
物理
数学分析
生态学
岩土工程
工程类
几何学
标识
DOI:10.1111/j.2042-7158.1998.tb06190.x
摘要
Abstract Extrapolation of animal data to assess pharmacokinetic parameters in man is an important tool in drug development. Clearance, volume of distribution and elimination half-life are the three most frequently extrapolated pharmacokinetic parameters. Extensive work has been done to improve the predictive performance of allometric scaling for clearance. In general there is good correlation between body weight and volume, hence volume in man can be predicted with reasonable accuracy from animal data. Besides the volume of distribution in the central compartment (Vc), two other volume terms, the volume of distribution by area (Vβ) and the volume of distribution at steady state (Vdss), are also extrapolated from animals to man. This report compares the predictive performance of allometric scaling for Vc, Vβ and Vdss in man from animal data. The relationship between elimination half-life (t 1/2) and body weight across species results in poor correlation, most probably because of the hybrid nature of this parameter. To predict half-life in man from animal data, an indirect method (CL = VK, where CL = clearance, V is volume and K is elimination rate constant) has been proposed. This report proposes another indirect method which uses the mean residence time (MRT). After establishing that MRT can be predicted across species, it was used to predict half-life using the equation MRT= 1.44 x t 1/2. The results of the study indicate that Vc is predicted more accurately than Vβ and Vdss in man. It should be emphasized that for first-time dosing in man, Vc is a more important pharmacokinetic parameter than Vβ or Vdss. Furthermore, MRT can be predicted reasonably well for man and can be used for prediction of half-life.
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