Physiology-Based Pharmacokinetic Modeling—Promise for Pediatric Drug Development?

Abstract

Physiologically based modeling has gained much interest from pharmaceutical industry. Prediction of pharmacokinetic properties based on physicochemical properties and in vitro data appears possible. Two applications are of high interest: the prediction of the pharmacokinetics before conducting first in man studies based on preclinical data, and the prediction of pharmacokinetics in children based on the pharmacokinetics in adults. To date, only a few investigations describing the prediction of the pharmacokinetics in children have been published. Some of these investigations showed data on the precision of these predictions by comparing the model with experimental pharmacokinetic data form clinical investigations in children. However, the method holds the promise of speeding up drug development in children, by rationalizing study planning and thus avoiding unnecessary clinical studies. This would ultimately save costs and more importantly, reduce the risks for children in clinical studies. Unfortunately, most of the work done in this field is not published, as investigations are conducted by the pharmaceutical industry during drug development. Therefore, it is difficult to assess the success rate of this approach. However, as practical experience is gained and knowledge on drug-metabolizing enzymes and drug transporters increases, the value of this approach will probably increase in the next few years.