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The paracetamol concentration‐effect relation in neonates
Author(s) -
Allegaert Karel,
Naulaers Gunnar,
Vanhaesebrouck Sophie,
Anderson Brian J
Publication year - 2013
Publication title -
pediatric anesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.704
H-Index - 82
eISSN - 1460-9592
pISSN - 1155-5645
DOI - 10.1111/pan.12076
Subject(s) - medicine , anesthesia , analgesic , pharmacodynamics , analysis of variance , repeated measures design , loading dose , pharmacokinetics , population , pharmacology , statistics , mathematics , environmental health
Summary Objectives We suggested a loading dose (20 mg·kg −1 ) followed by 10 mg·kg −1 q6h of intravenous ( IV ) paracetamol to achieve an effect compartment concentration of 11 mg·l −1 in neonates. Since there are no pharmacodynamic data to support such an effect compartment concentration, pain scores collected in neonates treated with an IV paracetamol loading dose (20 mg·kg −1 ) were used to validate this effect compartment concentration. Methods Pain scores (Leuven Neonatal Pain Score, LNPS , 0–14) before and 0.5, 1, 2, 3, 4, 5, and 6 h after IV paracetamol loading dose administration in neonates to whom IV paracetamol was administered as single analgesic ( PARANEO , www.clinicaltrials.gov , NCT 00969176) were collected. Trends were analyzed using repeated measures anova . An E max model with a delayed response compartment was fitted to data using population modeling. Results Nineteen of 60 neonates included in the PARANEO study received monotherapy with IV paracetamol to treat mild to moderate pain (e.g., alprostadil administration, delivery related trauma). Using repeated measures anova , there was a trend ( P = 0.02) for lower pain scores within 30 min after administration, with a slight increase in pain scores from 5 to 6 h. An E max model had a maximum effect of 4.15 pain units, an EC 50 of 2.07 mg·l −1 . Equilibration halftime ( T 1/2 keo) was 1.58 h. Conclusion Intravenous paracetamol is effective for moderate pain. An effect compartment concentration of 10 mg·l −1 (loading dose of 20 mg·kg −1 ) is associated with a pain score reduction of 3.4 LNPS units. This analysis suggests a similar paracetamol effect compartment concentration in neonates compared to children.