In:
Acta Paediatrica, Wiley, Vol. 94, No. 9 ( 2005-09), p. 1273-1279
Kurzfassung:
Background: Major changes in drug clearance and metabolism are observed during infancy, in part based on ontogenic regulation of various metabolic pathways. Since paracetamol provides a good substrate to study UGT (1A6) activity, urinary metabolites of propacetamol were determined in neonates in whom propacetamol was repeatedly administered. Methods: Paracetamol glucuronide (APAP‐G), paracetamol sulphate (APAP‐S) and free paracetamol were determined in urine samples of neonates during repeated administration of propacetamol. Spearman rank and linear multiple regression (MedCalc®, Mariakerke, Belgium) were used to study the effect of postnatal age, of postconceptional age and of repeated administration on the relative contribution of APAP‐G to overall urine paracetamol (APAP‐G+APAP‐S+free paracetamol) elimination (G/T ratio). Results: 147 samples were collected in 23 neonates. Molar median G/T ratio was 14% (range 1–53). Besides increasing G/T ratio with increasing postnatal ( p 〈 0.0001) and postconceptional age ( p 〈 0.01), repeated administration ( p 〈 0.01) also correlated with an increasing G/T ratio, and repeated administration remained significant ( p 〈 0.01) after correction of postnatal and postconceptional age in a multiple regression model. Conclusion: Major variability in the ontogeny of UGT activity to overall elimination of paracetamol was documented in neonates. Besides postnatal and postconceptional age, a significant effect of repeated administration on UGT activity was documented.
Materialart:
Online-Ressource
ISSN:
0803-5253
,
1651-2227
DOI:
10.1111/apa.2005.94.issue-9
DOI:
10.1111/j.1651-2227.2005.tb02088.x
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2005
ZDB Id:
1492629-5
ZDB Id:
1501466-6
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