The Utility of Pharmacometric Models in Clinical Pharmacology Research in Infants.

Abstract

Acquiring knowledge on drug disposition and action in infant is challenging because of the problem of sparse and unbalanced data obtained for each individual infant due to the limited blood volume as well as the issue of extensive inter-subject and intra-subject variability in drug exposure and response due to the fast growth and dynamic maturation changes in infants. This commentary highlights the importance of using population-based pharmacometric models to improve knowledge on drug disposition and action in infants. Pharmacometric modeling remains to be critical in clinical pharmacology research in infants. Many pediatric covariate models developed for scaling of drug clearance use a combination of allometric weight scaling to account for size change and a sigmoid function of antenatal development and postnatal maturation to characterize the age-related maturation. To expedite the development of safe and effective dosing regimens in infants, a number of strategies have been proposed recently, including the use of pediatric covariate model obtained from one drug for extrapolation to other drugs undergoing similar elimination pathways, as well as the combination of opportunistic clinical studies and population-based pharmacometrics models. Population-based pharmacometric modeling plays a pivotal role in clinical pharmacology research in infants. Most of the covariate models reported so far focus on antibiotics undergoing renal elimination. Novel modeling strategies have been proposed recently to facilitate clinical pharmacology research and expedite the dose optimization process in infants.