Print Email Facebook Twitter Observational infant exploratory [14C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis Title Observational infant exploratory [14C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis Author Garner, C.R. Park, K.B. French, N.S. Earnshaw, C. Schipani, A. Selby, A.M. Byrne, L. Siner, S. Crawley, F.P. Vaes, W.H.J. van Duijn, E. de ligt, R. Varendi, H. Lass, J. Grynkiewicz, G. Maruszak, W. Turner, M.A. Publication year 2015 Abstract Aims The aims of the study were to compare [14C]-paracetamol ([14C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group. Methods [14C]-PARA concentrations in 10-15 μl plasma samples were measured after enteral or i.v. administration of a single [14C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. Results Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h-1, 1.76 (1.07) l h-1, 2.93 (2.08) l h-1 and 2.72 (3.10) l h-1, t1/2 values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l-1 h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). Conclusions All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg-1) and a microdose (ng kg-1) in babies between 35 to 127 weeks post-menstrual age. [14C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies. © 2015 The British Pharmacological Society. Subject LifeMSB - Microbiology and Systems BiologyELSS - Earth, Life and Social SciencesHealthy for LifeBiologyHealthy LivingExploratory clinical studyMicrodosingPaediatric pharmacokineticsParacetamolUnclassified drugAccelerator mass spectrometryArea under the curveChildDrug blood levelDrug clearanceDrug half lifeFemaleHumanInfantMajor clinical studyMaleMass spectrometryMaximum plasma concentrationPharmacokineticsPlasma concentration-time curveTime to maximum plasma concentrationUltra performance liquid chromatographyVolume of distribution To reference this document use: http://resolver.tudelft.nl/uuid:64a7e42f-b2ad-489b-93c1-c3a60ea7b1ea DOI https://doi.org/10.1111/bcp.12597 TNO identifier 527065 ISSN 0306-5251 Source British Journal of Clinical Pharmacology, 80 (1), 157-167 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.