title: The paracetamol concentration-effect relation in neonates.
abstract: OBJECTIVE
  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, NCT00969176) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium. karel.allegaert@uz.kuleuven.ac.be
authors.forename: Karel
authors.initials: K
authors.lastname: Allegaert
authors.forename: Gunnar
authors.initials: G
authors.lastname: Naulaers
authors.forename: Sophie
authors.initials: S
authors.lastname: Vanhaesebrouck
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Anderson
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D010147:Pain Measurement / Q000379:methods / Q000706:statistics & numerical data; D010149:Postoperative Pain / Q000188:drug therapy
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen