Autor: |
Mooij, Miriam, Duijn, Esther, Knibbe, Catherijne, Allegaert, Karel, Windhorst, Albert, Rosmalen, Joost, Hendrikse, N., Tibboel, Dick, Vaes, Wouter, Wildt, Saskia, Mooij, Miriam G, van Duijn, Esther, Knibbe, Catherijne A J, Windhorst, Albert D, van Rosmalen, Joost, Hendrikse, N Harry, Vaes, Wouter H J, de Wildt, Saskia N |
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Zdroj: |
Clinical Pharmacokinetics; Oct2017, Vol. 56 Issue 10, p1185-1195, 11p |
Abstrakt: |
Background: We previously showed the practical and ethical feasibility of using [14C]-microdosing for pharmacokinetic studies in children. We now aimed to show that this approach can be used to elucidate developmental changes in drug metabolism, more specifically, glucuronidation and sulfation, using [14C]paracetamol (AAP).Methods: Infants admitted to the intensive care unit received a single oral [14C]AAP microdose while receiving intravenous therapeutic AAP every 6 h. [14C]AAP pharmacokinetic parameters were estimated. [14C]AAP and metabolites were measured with accelerator mass spectrometry. The plasma area under the concentration-time curve from time zero to infinity and urinary recovery ratios were related to age as surrogate markers of metabolism.Results: Fifty children [median age 6 months (range 3 days-6.9 years)] received a microdose (3.3 [2.0-3.5] ng/kg; 64 [41-71] Bq/kg). Plasma [14C]AAP apparent total clearance was 0.4 (0.1-2.6) L/h/kg, apparent volume of distribution was 1.7 (0.9-8.2) L/kg, and the half-life was 2.8 (1-7) h. With increasing age, plasma and urinary AAP-glu/AAP and AAP-glu/AAP-sul ratios significantly increased by four fold, while the AAP-sul/AAP ratio significantly decreased.Conclusion: Using [14C]labeled microdosing, the effect of age on orally administered AAP metabolism was successfully elucidated in both plasma and urine. With minimal burden and risk, microdosing is attractive to study developmental changes in drug disposition in children. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
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