Biosimulation is playing a growing role in drug development, espe­cially with candidate drugs intended to treat pediatric populations. Re­searchers want to minimize children’s exposure to experimental drugs. Therefore, they increasingly are turn­ing to physiologically-based phar­macokinetic (PBPK) modeling and biosimulation to provide insights into how a candidate drug might behave in younger subjects.

While it is possible to use allome­tric scaling to predict pediatric doses from adult data based on body size, differences in physiology can result in doses that are two or three times greater than necessary in infants.

PBPK modeling predicts more scientifically how a drug will behave in the body by integrating demo­graphic, physiological, biochemical and genetic systems data with drug absorption, metabolism and trans­portation data to simulate in vivo PK in virtual patient populations. This approach recognizes that PK changes with age by including information on how many of the systems parameters change with age. As a result, an anti-asthma drug can be eliminated very slowly in neonates but faster than an adult in a 2-year-old. Certara’s model recommends drug starting doses for children in specific age ranges.

Drug-drug interactions can also vary in magnitude between children and adults. An interaction that is greater than twofold in adults may be insignificant in infants. PBPK models can help to predict these differences.

FDA guidance currently only covers PBPK modeling for pediatric dose selection, but it has many other uses. We were able to demonstrate that the effective exposure for an oral sustained-dose medication would be the same for pediatric and adult pa­tients. We also showed that multiple doses of a drug were equivalent to one extended-release dose.

We expect to see well-validated PK results being increasingly included in pediatric new drug submissions and label extensions.

Trevor Johnson is principal scientist at Certara, the Princeton, N.J.-based global biosimulation technology-enabled drug development consultancy.

This article was reprinted from Volume 22, Issue 08, of The CenterWatch Monthly, an industry leading publication providing hard-hitting, authoritative business and financial coverage of the clinical research space. The Action Items section features short columns  focusing on actionable or how-to advice from clinical trial professionals. To submit an Action Item, please contact editorial@centerwatch.com. Subscribe >>