title: Population pharmacokinetics of high dose ibuprofen in cystic fibrosis.
abstract: OBJECTIVE
  To evaluate ibuprofen population pharmacokinetics in a large series of data collected in children with cystic fibrosis (CF) treated with high doses of ibuprofen (59 patients; 2-18 years), and to identify the main causes responsible for the considerable interindividual variability in ibuprofen serum levels.
  
  
  METHODS
  Blood samples were collected during routine clinical care; serum ibuprofen concentrations were determined by HPLC. Fitting of the concentration/time data to a one compartment kinetic population model was performed by a non-linear mixed effect regression method.
  
  
  RESULTS
  Body weight, dose, and ibuprofen dosage form (lysinate salt or the free acid form), for elimination clearance (CL/F); and body weight, dose, and fasting status for the apparent distribution volume (Vd/F) proved to be the covariates with influence in the model. The four factors identified helped to explain part of the interindividual variability observed, but the remaining unexplained variability made therapeutic drug monitoring absolutely essential.
authors.affiliation: Biochemical Service, Ramón y Cajal Hospital, Madrid, Spain. marranz@hrc.insalud.es
authors.forename: I
authors.initials: I
authors.lastname: Arranz
authors.forename: A
authors.initials: A
authors.lastname: Martín-Suárez
authors.forename: J M
authors.initials: JM
authors.lastname: Lanao
authors.forename: F
authors.initials: F
authors.lastname: Mora
authors.forename: C
authors.initials: C
authors.lastname: Vázquez
authors.forename: A
authors.initials: A
authors.lastname: Escribano
authors.forename: M
authors.initials: M
authors.lastname: Juste
authors.forename: J
authors.initials: J
authors.lastname: Mercader
authors.forename: E
authors.initials: E
authors.lastname: Ripoll
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy*; D005215:Fasting; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen