title: Population pharmacokinetics of omeprazole in critically ill pediatric patients.
abstract: BACKGROUND
  To develop a population pharmacokinetic model for intravenous omeprazole in critically ill children.
  
  
  METHODS
  One hundred eighty-six omeprazole concentration-time data from 40 critically ill children were analyzed using the nonlinear mixed-effects approach with the nonlinear mixed-effects modeling software, version 7.2 software. Patients were randomized into 2 groups and received intravenous omeprazole at a dose of 0.5 or 1 mg/kg twice daily. Blood samples were drawn at 0.5, 2, 6, 12, 24, and 48 hours after the first infusion.
  
  
  RESULTS
  The pharmacokinetic profile was best described by a 2-compartment model with a first-order elimination process. Between-patient variability could only be associated with plasma clearance (CL). The typical values for plasma CL were 24.9 L·h·70 kg (10.08%), with a distributional clearance of 53.9 L·h·70 kg (11.00%) and central and peripheral compartment distribution volumes of 4.23 L/70 kg (19.62%) and 674 L/70 kg (0.89%), respectively. Allometric size models seemed to predict changes adequately in all the pharmacokinetic parameters. High values of between-patient variability of CL [75.50% (2.60%)] and residual variability [130.0% (5.26%)] were still found in the final model. Model-based simulations suggested that the most suitable dose was 1 mg/kg because this yielded similar exposure (defined by the area under the concentration-time curve) to that obtained in adults after a 20-mg dose of omeprazole intravenously.
  
  
  CONCLUSIONS
  An allometric size model allows changes to be predicted in all the pharmacokinetic parameters, making dose adjustment by body weight important to achieve the most effective omeprazole exposure. This is the first step toward a population pharmacokinetic study, including more data to develop a predictable model to be used during therapeutic drug monitoring.
authors.affiliation: *Paediatric Intensive Care Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain; †Biopharmacy and Pharmacokinetics Department, School of Pharmacy, University of Barcelona, Spain; and ‡Pharmacy Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Solana
authors.forename: Helena
authors.initials: H
authors.lastname: Colom
authors.forename: Jesús
authors.initials: J
authors.lastname: López-Herce
authors.forename: Javier
authors.initials: J
authors.lastname: Urbano
authors.forename: Rafael
authors.initials: R
authors.lastname: González
authors.forename: Jorge
authors.initials: J
authors.lastname: López
authors.forename: Cecilia
authors.initials: C
authors.lastname: Manzanares
authors.forename: Angel
authors.initials: A
authors.lastname: Carrillo
mesh_terms: D019540:Area Under Curve; D001835:Body Weight / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D009853:Omeprazole / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011446:Prospective Studies
chemical_list: D009853:Omeprazole