Pediatric Microdose Study of ( 14 C)Paracetamol to Study Drug Metabolism Using Accelerated Mass Spectrometry: Proof of Concept Miriam G. MooijEsther van DuijnCatherijne A. J. KnibbeAlbert D. Windhorst • N. Harry HendrikseWouter H. J. VaesEdwin SpaansBabs O. Fabriek • Hugo SandmanDimitri GrossouwLidwien M. HanffPaul J. J. M. Janssen • Birgit C. P. KochDick TibboelSaskia N. de Wildt

Background Pediatric drug development is hampered by practical, ethical, and scientific challenges. Microdosing is a promising new method to obtain pharmacokinetic data in children with minimal burden and minimal risk. The use of a labeled oral microdose offers the added benefit to study intestinal and hepatic drug disposition in children already receiving an intravenous therapeutic drug dose for clinical reasons. Objective The objective of this study was to present pilot data of an oral [ 14 C]paracetamol [acetaminophen (AAP)] microdosing study as proof of concept to study developmental pharmacokinetics in children. Methods In an open-label microdose pharmacokinetic pilot study, infants (0‐6 years of age) received a single oral [ 14 C]AAP microdose (3.3 ng/kg, 60 Bq/kg) in addition to intravenous therapeutic doses of AAP (15 mg/kg intravenous every 6 h). Blood samples were taken from an indwelling catheter. AAP blood concentrations were measured by liquid chromatography‐tandem mass spectrometry (LC-MS/MS) and [ 14 C]AAP and metabolites ([ 14 C]AAP-Glu and [ 14 C]AAP-4Sul) were measured by