Background: Major changes in drug clearance and metabo-lism are observed during infancy, in part based on ontogenic regulation of various metabolic pathways. Since para-cetamol provides a good substrate to study UGT (1A6) act-ivity, 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 (MedCale , 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. Background: Major changes in drug clearance and metabo-lism are observed during infancy, in part based on ontogenic regulation of various metabolic pathways. Since para-cetamol provides a good substrate to study UGT (1A6) act-ivity, 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 MedCale, 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) Repeated administration (P <0.01) also correlated with an increasing G / T ratio, and repeated administration was significant (P <0.01) after correction of postnatal and postconceptional age in a multiple (P <0.01) 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.