Toutain P L, Bousquet-Mélou A
UMR 181 Physiopathologie et Toxicologie Expérimentales INRA/ENVT, Ecole Nationale Vétérinaire de Toulouse, Toulouse cedex 03, France.
J Vet Pharmacol Ther. 2004 Dec;27(6):441-53. doi: 10.1111/j.1365-2885.2004.00602.x.
Volumes of distribution are proportionality constants between total amount of drug in the body and plasma concentrations. As snapshot plasma drug concentrations may be measured in different conditions (at equilibrium, under pseudo-equilibrium condition,...), several volumes of distribution have been defined. The two most relevant are the volume of distribution at equilibrium (V(ss)), and the volume of distribution during pseudo-equilibrium (V(area)). Volumes of distribution are used to compute a loading dose (V(ss)) or the residual amount of drug in the body knowing plasma concentrations (V(area)). Volume of distribution may be interpreted in terms of drug distribution having recourse to physiological models involving drug binding to plasma and tissues. Volumes of distribution should be determined early in drug development programmes and those having a large volume of distribution may be selected to obtain a long terminal half-life even for drugs having a relatively high clearance.
分布容积是体内药物总量与血浆浓度之间的比例常数。由于可以在不同条件下(平衡时、伪平衡条件下等)测量即时血浆药物浓度,因此定义了几种分布容积。最相关的两种是平衡分布容积(V(ss))和伪平衡期间的分布容积(V(area))。分布容积用于计算负荷剂量(V(ss))或已知血浆浓度时体内的药物残留量(V(area))。分布容积可以通过涉及药物与血浆和组织结合的生理模型来解释药物分布情况。应在药物研发计划的早期确定分布容积,对于清除率相对较高的药物,可选择分布容积大的药物以获得较长的末端半衰期。