TNO is one of the partners of Topsector Life Sciences & Health. With their PAMPER project they focus on microdosing of drugs in children.

Still little is known about the effectiveness and safety of drugs in children. Despite increased attention for drug research through legislation and public funding, almost half of medicines is still prescribed off-label to children. Microdosing is a promising technique, providing a new and safe way to investigate the disposition (pharmacokinetics) of drugs in children. This could help to personalize drug dosages for specific age groups in children.

Microdosing builds on the basic principle of toxicology: ‘dosis facit venenum’, meaning that the dosage defines whether a substance is toxic or not.  With the microdosing technique extremely low dosages of drugs can be administered. A specialized device, the Accelerator Mass Spectometry (AMS) can determine the plasma levels of even these low dosages of drugs for pharmacokinetic studies. In Europe, the AMS technology is only available at TNO Zeist.

Microdosing creates new possibilities to carry out pharmacokinetic studies in pediatric populations with existing and new drugs, while simultaneously meeting the requirements of minimized risk and load. In particular, the low dosages of the drug, combined with the very low radioactivity, now enable us to carry out such studies with minimal risk. The pharmacokinetics of a drug are important because the absorption and residence time of a drug in the human body are crucial factors for the effectiveness. A major advantage is that with a limited set of studies in which the age-dependent development of the activity of key enzymes is examined, pharmacokinetics can be determined for a large part of existing drugs.

In addition to the Pamper project, Erasmus MC Sophia Children’s Hospital and TNO are applying the microdosing technology in a ZonMW funded study, in order to map the age-dependent activity of a specific drug metabolism in the intestine and liver. First results show that it is ethical and practical, and scientifically possibly to conduct microdosing studies in children.