title: Pharmacokinetics and analgesic effectiveness of intravenous parecoxib for tonsillectomy ± adenoidectomy.
abstract: BACKGROUND
  Few pharmacokinetic (PK) and pharmacodynamic (PD) data exist for COX-2 selective inhibitors in children. We wished to characterize the PKPD of parecoxib and its active metabolite, valdecoxib, in this population.
  
  
  METHODS
  Children (n = 59) were randomized to parecoxib 0.25 mg·kg-1, 1 mg·kg-1, and 2 mg·kg-1during tonsillectomy ± adenoidectomy. Samples (4-6 per child) were obtained from indwelling cannula over 6 h. A second group of inpatient children (n = 15) given 1 mg·kg-1contributed PK data from 6 to 24 h. Pain scores and rescue medication for the first group were recorded postoperatively for up to 24 h. PK data were pooled with those (10 samples/24 h) from a published study of children (n = 38) who underwent surgery. A three-compartment parent and one-compartment metabolite model with first-order elimination was used to describe data using nonlinear mixed effects models. An EMAXmodel described the relationship between dose and rescue morphine equivalents during recovery.
  
  
  RESULTS
  Parecoxib PK parameter estimates were CLPARECOXIB19.1 L·h-1·70 kg-1, V1PARECOXIB4.2 L·70 kg-1, Q2PARECOXIB6.29 L·h-1·70 kg-1, V2PARECOXIB130 L·70 kg-1, Q3PARECOXIB6.02 L·h-1·70 kg-1, and V3PARECOXIB2.03 L·70 kg-1. We assumed all parecoxib was metabolized to valdecoxib with CLVALDECOXIB9.53 L·h-1·70 kg-1and VVALDECOXIB51 L·70 kg-1. There was no maturation of clearance over the age span studied. There were no differences in pain scores between groups on waking, discharge, 12 h, or 24 h. There were no differences in analgesia consumption over 24 h between groups for tramadol, fentanyl, and morphine rescue use. Fentanyl and morphine consumption, expressed as morphine equivalents (0.13 mg·kg-1) in the 0.25 mg·kg-1group, was greater than that observed in the 1 or 2 mg·kg-1groups (0.095 mg·kg-1) in PACU.
  
  
  CONCLUSIONS
  Parecoxib 0.9 mg·kg-1in a 2-year-old, 0.75 mg·kg-1in a 7-year-old, and 0.65 mg·kg-1in a 12-year-old child achieves dose equivalence of 40 mg in a standard 70 kg person. Clearance maturation may occur in infants younger than the current cohort. Parecoxib doses above 1 mg·kg-1add no additional analgesia.
authors: Department of Anaesthesia, Starship Children's Hospital, Auckland, New Zealand.
authors: Lena
authors: L
authors: Tan
authors: Department of Anaesthesia, Starship Children's Hospital, Auckland, New Zealand.
authors: Elsa
authors: E
authors: Taylor
authors: Department of Anaesthesiology, University of Auckland, Auckland, New Zealand.
authors: Jacqueline A
authors: JA
authors: Hannam
authors: Department of Otolaryngology, Starship Children's Hospital, Auckland, New Zealand.
authors: Lesley
authors: L
authors: Salkeld
authors: School of Medicine & Pharmacology, University of Western Australia, Perth, WA, Australia.
authors: Sam
authors: S
authors: Salman
authors: Department of Anaesthesia, Starship Children's Hospital, Auckland, New Zealand.|Department of Anaesthesiology, University of Auckland, Auckland, New Zealand.
authors: Brian J
authors: BJ
authors: Anderson
mesh_terms: D000233:Adenoidectomy; D000293:Adolescent; D000698:Analgesia / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D052246:Cyclooxygenase 2 Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000493:pharmacokinetics*; D008297:Male; D010149:Postoperative Pain / Q000188:drug therapy*; D014068:Tonsillectomy; D016896:Treatment Outcome
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; C409945:parecoxib
keywords: anesthesia; nonsteroidal anti-inflammatory drug; pain; pharmacodynamics; pharmacokinetics; tonsillectomy ± adenoidectomy