Towards a better understanding of the developmental changes in pediatric intestinal drug transport

Most drugs prescribed to children are given orally, but major knowledge gaps remain in our understanding of age-related changes in drug absorption. This hampers adequate dosing in children. In this public-private partnership Radboudumc, Erasmus MC and UCB Pharma collaborated to not only develop methods but also create new data to better understand drug absorption in children.

By better understanding the impact of age on drug metabolism and drug transport in the intestine, doses can be optimised to give children the right dose, resulting in the most effective and safe drug dose.

In this project, two innovative techniques were developed to study drug absorption, using human tissue to reduce the need for animal studies. First, teh consortium used proteomics, a very sensitive method, to measure in small amounts of pediatric and surgical left-over intestinal tissue the amount of drug metabolising enzymes and transporters. Second, they also developed the Ussing method, to measure active drug transport over the intestine in the same pediatric and adult tissues.

The consortium thereby elucidated that these enzymes and transporters change with age. Interesting, these changes are not the same for all enzymes and transporters but show different patterns. These specific age-related changes can now be used in so called physiology-based pharmacokinetic models, ‘virtual children’ to predict individualized doses for children across the pediatric age range. The Ussing model and the proteomics methods will now be used to further study drug absorption in children and adults, including in organoids, ‘mini-organs’ which are now developed in a follow-up project.

NPO Klokhuis video on drug absorption from the intestine was filmed at the RadboudUMC, broadcasted by NTR. The video is available online: https://www.hetklokhuis.nl/tv-uitzending/4301/Pijnstillers.