28-05-2011, 09:52 AM
Abstract
Interspecies allometric scaling, based on the assumption that a change in pharmacokinetic parameters correlates closely with body weight, can be described as an operation when a pharmacokinetic parameter of interest is scaled across species. This method has become a useful instrument in drug development, especially at the preclinical discovery stage, because the extrapolation facilitates the process of dosing transitions from animals to man and accelerates the drug testing and approval process. For greater extrapolation accuracy of allometric scaling of drug doses, species differences in pharmacokinetic parameters should be taken into account. The three most important pharmacokinetic parameters for extrapolation are clearance, volume of distribution, and elimination half-life. Clearance plays a significant role in interspecies allometric scaling as the predicted clearance can be applied in estimating a first-in-human dose. Through the years, many approaches have been proposed to improve the accuracy of the prediction. Research studies indicate that there are different degrees of success with different methods for different drugs. Furthermore, the adaptation of interspecies scaling is also a very useful tool in enhancing the therapeutic dosage selection in veterinary medicine. However, it is important to consider how to reduce the risk of extrapolation errors that can seriously affect the safety and therapeutic response. All in all, the interspecies scaling still requires continuous development and clearer comprehension. With the proper method selection and understanding of allometric scaling, its rational application to human and veterinary medicine will prove to be time and cost effective in drug development.
