title: Pharmacokinetics of single-dose intravenous ketorolac in infants aged 2-11 months.
abstract: BACKGROUND
  Ketorolac is a parenterally available nonsteroidal antiinflammatory drug that nonselectively inhibits cyclooxygenase. Ketorolac is an attractive alternative to opioids in the pediatric population because of its favorable side effect profile; it provides postoperative analgesia similar to morphine, but is associated with significantly less respiratory depression, pruritus, and emesis. Despite the efficacy of ketorolac in young patients, there are minimal data to characterize the pharmacokinetic variables of ketorolac in infants younger than 6 months.
  
  
  METHODS
  In this study, 17 infants younger than 1 year old, without renal or liver disease, undergoing elective surgery received a single-dose of IV ketorolac 0.5 mg/kg. Blood was sampled at 0, 5, 10, 15, 30, 60, and 120 minutes, and at 4, 6, 12, and 24 hours. Ketorolac levels were analyzed using a specific and validated high-performance liquid chromatography method with mass spectrometry (LC-LC/MS/MS). Pharmacokinetic analysis of individual subjects and population pharmacokinetic modeling was performed using SAAM II and PopKinetics, respectively (SAAM Institute, University of Washington).
  
  
  RESULTS
  Characterization of pharmacokinetic parameters was possible in 14 subjects. The data were best described by a 2-compartment model. Estimated individual parameters were clearance 1.49 ± 1.12 mL/min/kg, Vss (volume of distribution at steady state) 0.31 ± 0.11 L/kg, and half-life of 236 ± 169 minutes. Estimated population pharmacokinetic parameters were clearance 1.52 mL/min/kg and Vss 0.29 L/kg. There was a trend toward lower clearances in younger patients.
  
  
  CONCLUSIONS
  This is the first report of individualized pharmacokinetic parameters of ketorolac in children in which the majority of subjects were younger than 6 months old.
authors.affiliation: Department of Anesthesiology, The Children's Hospital, 13123 East 16th Ave., B090, Aurora, CO 80045, USA. mindycohenmd@gmail.co
authors.forename: Mindy N
authors.initials: MN
authors.lastname: Cohen
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
authors.forename: Thomas
authors.initials: T
authors.lastname: Henthorn
authors.forename: Zung
authors.initials: Z
authors.lastname: Vu Tran
authors.forename: Vanessa
authors.initials: V
authors.lastname: Moll
authors.forename: Jeannie
authors.initials: J
authors.lastname: Zuk
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Galinkin
mesh_terms: D000367:Age Factors; D017558:Elective Surgical Procedures / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D020910:Ketorolac / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D010149:Postoperative Pain / Q000378:metabolism* / Q000517:prevention & control*
chemical_list: D020910:Ketorolac