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 (...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.展开更多
The aim of this study was to document the pharmacodynamics of chloral hydrate in former preterm infants at term post-conception age. The degree of sedation (COMFORT), feeding behaviour and cardiorespiratory events (br...The aim of this study was to document the pharmacodynamics of chloral hydrate in former preterm infants at term post-conception age. The degree of sedation (COMFORT), feeding behaviour and cardiorespiratory events (bradycard-ic events, apnoeas) before and after administration of chloral hydrate (oral, 30 mg/kg) were prospectively eva-luated in former preterm infants during procedural sedation. Characteristics at birth, during neonatal stay and at inclusion were collected. Paired Wilcoxon and McNemar tests were used to study the impact of chloral hydrate. Characteristics of infants who displayed severe bradycardic events were compared to infants in whom no bradycardic events were recorded (MannWhitney U, Fischer’s exact). A significant increase in sedation (decrease COMFORT scale) was observed up to 12 h after administration. There was a minor but significant decrease in oral intake (161 to 156 ml/kg/day, P < 0.01). A significant increase in the number of bradycardic events (< 80/min: 38 to 82 events, of which < 70/min: 30 to 79 of which < 60/min: 15 to 45; at least P < 0.01) and in the duration of the most severe bradycardic event (8- 12.5 s) was observed. Therefore, further inclusion was stopped when 26 neonates were included. Infants who displayed severe bradycardic (< 60/min) events ( n=13) after administration of chloral hydrate had a lower gestational age at birth without difference in post-conception age at inclusion. Conclusion: Chloral hydrate was associated with an increase in unintended side-effects in former preterm infants, likely reflecting population specific pharmacodynamics and kinetics of chloral hydrate.展开更多
The effect of prophylactic administration of ibuprofen on the cerebral circulation in preterm babies was measured with near infrared spectroscopy. No significant difference in the change in cerebral blood volume, chan...The effect of prophylactic administration of ibuprofen on the cerebral circulation in preterm babies was measured with near infrared spectroscopy. No significant difference in the change in cerebral blood volume, change in cerebral blood flow, or tissue oxygenation index was found between administration of ibuprofen or placebo.展开更多
文摘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.
文摘The aim of this study was to document the pharmacodynamics of chloral hydrate in former preterm infants at term post-conception age. The degree of sedation (COMFORT), feeding behaviour and cardiorespiratory events (bradycard-ic events, apnoeas) before and after administration of chloral hydrate (oral, 30 mg/kg) were prospectively eva-luated in former preterm infants during procedural sedation. Characteristics at birth, during neonatal stay and at inclusion were collected. Paired Wilcoxon and McNemar tests were used to study the impact of chloral hydrate. Characteristics of infants who displayed severe bradycardic events were compared to infants in whom no bradycardic events were recorded (MannWhitney U, Fischer’s exact). A significant increase in sedation (decrease COMFORT scale) was observed up to 12 h after administration. There was a minor but significant decrease in oral intake (161 to 156 ml/kg/day, P < 0.01). A significant increase in the number of bradycardic events (< 80/min: 38 to 82 events, of which < 70/min: 30 to 79 of which < 60/min: 15 to 45; at least P < 0.01) and in the duration of the most severe bradycardic event (8- 12.5 s) was observed. Therefore, further inclusion was stopped when 26 neonates were included. Infants who displayed severe bradycardic (< 60/min) events ( n=13) after administration of chloral hydrate had a lower gestational age at birth without difference in post-conception age at inclusion. Conclusion: Chloral hydrate was associated with an increase in unintended side-effects in former preterm infants, likely reflecting population specific pharmacodynamics and kinetics of chloral hydrate.
文摘The effect of prophylactic administration of ibuprofen on the cerebral circulation in preterm babies was measured with near infrared spectroscopy. No significant difference in the change in cerebral blood volume, change in cerebral blood flow, or tissue oxygenation index was found between administration of ibuprofen or placebo.
