title: The pharmacokinetics of ketorolac after single postoperative intranasal administration in adolescent patients.
abstract: BACKGROUND
  Ketorolac tromethamine (ketorolac) administration reduces postoperative opioid requirements. The pharmacokinetic characteristics of intranasal ketorolac tromethamine in children have not been characterized. Our objective of this study was to determine the pharmacokinetics of a single intranasal dose of ketorolac in adolescent patients.
  
  
  METHODS
  Twenty surgical patients, ages 12 to 17 years, were enrolled. After surgery, subjects received intranasal ketorolac 15 mg (weight ≤50 kg) or 30 mg (weight >50 kg) using a proprietary administration system. Blood samples were obtained for ketorolac assay at baseline (within 15 minutes before the dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after the dose. A population analysis was undertaken using nonlinear mixed-effects models. Parameter estimates were standardized to a 70-kg person.
  
  
  RESULTS
  The intranasal dosing in adolescents was well tolerated with minimal adverse effects. A 1-compartment model with first-order absorption and elimination was satisfactory to describe time-concentration profiles. Population parameter estimates (between subject variability) were clearance (CL/F) 2.05 L/h (60.5%), volume of distribution (V/F) 15.2 L (32.4%), absorption half-life (t(1/2)abs) 0.173 hour (25.0%). Time to peak concentration (Tmax) was 52 minutes (SD 6 minutes).
  
  
  CONCLUSIONS
  Administration of ketorolac by the intranasal route resulted in a rapid increase in plasma concentration and may be a useful therapeutic alternative to IV injection in adolescents because plasma concentrations attained with the device are likely to be analgesic (investigational new drug no. 62,829).
authors.affiliation: Department of Anesthesia, Stanford University, Palo Alto, California, USA. ddrover@stanford.edu
authors.forename: David R
authors.initials: DR
authors.lastname: Drover
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Hammer
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Anderson
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000367:Age Factors; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001835:Body Weight; D002648:Child; D003198:Computer Simulation; D005260:Female; D006801:Humans; D020911:Ketorolac Tromethamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D011182:Postoperative Care
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020911:Ketorolac Tromethamine