Print Email Facebook Twitter Pediatric Microdose Study of [14C]Paracetamol to Study Drug Metabolism Using Accelerated Mass Spectrometry: Proof of Concept Title Pediatric Microdose Study of [14C]Paracetamol to Study Drug Metabolism Using Accelerated Mass Spectrometry: Proof of Concept Author Mooij, M.G. van Duijn, E. Knibbe, C.A.J. Windhorst, A.D. Hendrikse, N.H. Vaes, W.H.J. Spaans, E. Fabriek, B.O. Sandman, H. Grossouw, D. Hanff, L.M. Janssen, P.J.J.M. Koch, B.C.P. Tibboel, D. de Wildt, S.N. Publication year 2014 Abstract Results: Ten infants (aged 0.1–83.1 months) were included; one was excluded as he vomited shortly after administration. In nine patients, [14C]AAP and metabolites in blood samples were detectable at expected concentrations: median (range) maximum concentration (Cmax) [14C]AAP 1.68 (0.75–4.76) ng/L, [14C]AAP-Glu 0.88 (0.34–1.55) ng/L, and [14C]AAP-4Sul 0.81 (0.29–2.10) ng/L. Dose-normalized oral [14C]AAP Cmax approached median intravenous average concentrations (Cav): 8.41 mg/L (3.75–23.78 mg/L) and 8.87 mg/L (3.45–12.9 mg/L), respectively. Conclusions: We demonstrate the feasibility of using a [14C]labeled microdose to study AAP pharmacokinetics, including metabolite disposition, in young children. 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. Methods: In an open-label microdose pharmacokinetic pilot study, infants (0–6 years of age) received a single oral [14C]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 [14C]AAP and metabolites ([14C]AAP-Glu and [14C]AAP-4Sul) were measured by accelerator mass spectrometry. Objective: The objective of this study was to present pilot data of an oral [14C]paracetamol [acetaminophen (AAP)] microdosing study as proof of concept to study developmental pharmacokinetics in children. Subject LifeRAPID - Risk Analysis for Products in DevelopmentELSS - Earth, Life and Social SciencesFood and NutritionNutritionHealthy LivingCarbon 14Drug metaboliteParacetamolAccelerator mass spectrometryBlood samplingChildClinical articleDrug blood levelDrug metabolismFemaleHumanIndwelling catheterInfantLimit of quantitationLiquid chromatographyMaleMass spectrometryMaximum plasma concentrationNewbornOpen studyPharmacokineticsPilot studyPreschool childPriority journalSingle drug doseTime to maximum plasma concentration To reference this document use: http://resolver.tudelft.nl/uuid:a7de5a0b-a115-4f8f-81be-3cf8b0f2eaf1 DOI https://doi.org/10.1007/s40262-014-0176-8 TNO identifier 522542 ISSN 0312-5963 Source Clinical Pharmacokinetics, 53 (11), 1045-1051 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.