This chapter describes different techniques and approaches to predict pharmacokinetic parameters from animals to humans during drug development. These techniques are useful and if used with proper understanding, it will be time and cost effective. The chapter illustrates the advantages and the limitations of allometric scaling.

Allometry is based on the assumption that the relationship between anatomy and physiologic functions is similar among mammalian species [1, 2]. Over the years, allometry has become a useful tool for correlating pharmacokinetic parameters with body weight from different animal species. By establishing such a correlation, one can predict pharmacokinetic parameters in humans which can be useful during drug development. Interspecies scaling to predict pharmacokinetic parameters in humans can be performed by two approaches:

i. physiologically based method (PB-PK), ii. empirical allometric method.

Physiological method, however, has found only limited use in drug discovery and development, because this approach is costly, mathematically complex, and time consuming.

On the other hand, the allometric approach though empirical, is less complicated and easy to use than the physiologically based method. The anatomical, physiological, and biochemical similarities among animals can be generalized and expressed mathematically by the allometric equation. The allometric approach has been based on the power function, as the body weight from several species is plotted against the pharmacokinetic parameter of interest on a log-log scale. The power function is written as follows:

where Y is the parameter of interest, W is the body weight, and a and b are the coefficient and exponent of the allometric equation, respectively. The log transformation of Eq. (1) is represented as follows:

where log a is the y-intercept, and b is the slope.

Besides, using the power function to establish a relationship between a pharmacokinetic parameter of interest and body weight, the power equation has also been used to establish relationship between body weight and physiologic parameters such as liver weight, liver blood flow, kidney weight, kidney blood flow, and glomerular filtration rate of several species including humans [3].

Using allometric approach, many pharmacokinetic parameters such as clearance (CL), volume of distribution (V), elimination half-life (t1/2), and absolute bioavailability (F) from animals to humans have been predicted [3]. The following sections will describe several allometric approaches to predict these parameters from animals to humans.

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