Man versus beast: pharmacokinetic scaling in mammals.

Land mammals range in size from the 3-g shrew to the 3000-kg elephant. Despite this 10(6) range in weight, most land mammals have similar anatomy, physiology, biochemistry, and cellular structure. This similarity has allowed interspecies scaling of physiologic properties such as heart rate, blood flow, blood volume, organ size, and longevity. The equation that is the basis for scaling physiologic properties among mammals is the power equation Y = aWb, where Y is the physiologic variable of interest, W is body weight, and log a is the y-intercept and b is the slope obtained from the plot of log Y versus log W. Animals commonly used in preclinical drug studies (i.e., mice, rats, rabbits, monkeys, and dogs) do not eliminate drugs at the same rate that humans eliminate drugs; small mammals usually eliminate drugs faster than large mammals. Since drug elimination is intimately associated with physiologic properties that are well described among species, it seems reasonable to surmise that drug elimination can be scaled among mammals. Analysis of drug pharmacokinetics in numerous species demonstrates that drug elimination among species is predictable and, in general, obeys the power equation Y = aWb. Early papers on interspecies pharmacokinetic scaling normalized the x- and y-axes to illustrate the superimpossibility of pharmacokinetic curves from different species. More recently, the x- and y-axes have been left in the common units of concentration and time, and individual pharmacokinetic variables have been adjusted to predict pharmacokinetic profiles in an untested species, usually humans.