ABSTRACT
Allometric scaling has been shown to be a good predictor of a variety of biological rates, times, and dimensions (including metabolic rate, lifespan, growth rate, heart rate, DNA nucleotide substitution rates, and length of aortas) between species of several orders of magnitude in body weight (Schmidt-Nielsen, 1984; West et al., 1997, 1999b; West and Brown, 2004, 2005). It is not surprising that allometric scaling principles can provide useful guidance for the scaling preclinical evaluation of drug metabolism and response (Boxenbaum, 1982; Gronert et al., 1995; Hu and Hayton, 2001; Lepist and Jusko, 2004; Zuideveld et al., 2007). Most of the work in allometric scaling of pharmacokinetic (PK) and pharmacodynamic (PD) responses was motivated to predict the time course of drug effects in man using the data observed in animals. Limited attention has been given to the use of allometric scaling to enhance an understanding of the genetic regulation of PK and PD reactions, and ultimately to predict the time courses of drug concentrations and drug effects.
