Ethical considerations prevent extensive clinical trials in pediatric populations;however, with the use of PBPK modeling, in vivo data from adults can be used to explore the mechanisms of drug disposition and pharmacokinetics (PK) in children following a variety of administration routes.Simulation tools allow exploring the sensitivity of exposure to individual processes involved in drug absorption, distribution, and elimination,and so can help in design of the trials to maximize their efficiency.Several studies were published in the past demonstrating the accuracy of PBPK models in predicting pediatric PK for compounds with simple (perfusion-limited) tissue distribution and elimination mainly by CYP metabolism.