Upton Richard N
Discipline of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, North Terrace, Adelaide, SA 5005, Australia.
J Pharmacol Toxicol Methods. 2008 Nov-Dec;58(3):198-205. doi: 10.1016/j.vascn.2008.08.001. Epub 2008 Aug 13.
Physiological approaches to pharmacokinetic analysis require data on organ sizes and organ blood flows for a given species. An internally consistent compilation of these data for sheep and pigs is needed. Furthermore, it is desirable to be able to appropriately scale these data for individuals of different sizes to simulate hypothetical populations of sheep or pigs for pharmacokinetic/pharmacodynamic modelling.
The literature was reviewed and tables of organ size (as a ratio of body weight) and organ perfusion (flow in ml/min per 100 g of tissue) were compiled for sheep and pigs of a standard size. Equivalent data for man were compiled using the P(3)M program for comparison. The standard size for sheep, pig and man were 45, 25 and 69 kg, respectively. Allometric scaling was used to modify the standard size data for body size, and the equations for doing so were coded in a small computer program. This program was tested by comparison with published sheep data (body weights 5-55.5 kg).
The three species differed mostly in the percentage of cardiac output going to the liver (47% for the sheep, 31% for the pig, 23% for man). The distribution of body weight in sheep could be simulated by assuming a log-normal distribution (mean 45 kg, log SD 0.12), with the ratio of organ size to body weight being normally distributed with a coefficient of variation of 8%. The distribution of cardiac output could be simulated by assuming that organ perfusion varied around the standard size value with a coefficient of variation of 35% and an allometric scaling coefficient of 0.75.
The compiled data and code are suitable for physiological pharmacokinetic/pharmacodynamic modelling of data collected using sheep and pigs.
药代动力学分析的生理学方法需要给定物种的器官大小和器官血流量数据。需要对绵羊和猪的这些数据进行内部一致的汇编。此外，希望能够针对不同大小的个体对这些数据进行适当缩放，以模拟用于药代动力学/药效学建模的假设绵羊或猪种群。
查阅文献，为标准大小的绵羊和猪编制了器官大小（作为体重的比例）和器官灌注（每100克组织的毫升/分钟流量）表。使用P(3)M程序编制了人类的等效数据以供比较。绵羊、猪和人类的标准大小分别为45、25和69千克。采用异速生长缩放法对标准大小数据进行体型修正，并将相关方程编码到一个小型计算机程序中。通过与已发表的绵羊数据（体重5 - 55.5千克）进行比较来测试该程序。
这三个物种在流向肝脏的心输出量百分比方面差异最大（绵羊为47%，猪为31%，人类为23%）。假设绵羊体重呈对数正态分布（均值45千克，对数标准差0.12），器官大小与体重的比例呈正态分布，变异系数为8%时，可以模拟绵羊体重的分布。假设器官灌注围绕标准大小值变化，变异系数为35%，异速生长缩放系数为0.75时，可以模拟心输出量的分布。
汇编的数据和代码适用于对使用绵羊和猪收集的数据进行生理药代动力学/药效学建模。
