Application of Population Pharmacokinetic Modeling for Individualized Infliximab Dosing Strategies in Crohn Disease

Adam Frymoyer, Daniël R. Hoekman, Travis L. Piester, Tim G. De Meij, Thalia Z. Hummel, Marc A. Benninga, Angelika Kindermann, K. T. Park

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)


Objectives:The pharmacokinetics of infliximab (IFX) is highly variable in children with Crohn disease (CD), and a one-size-fits-all approach to dosing is inadequate. Model-based drug dosing can help individualize dosing strategies. We evaluated the predictive performance and clinical utility of a published population pharmacokinetic model of IFX in children with CD.Methods:Within a cohort of 34 children with CD who had IFX trough concentrations measured, the pharmacokinetics of each patient was estimated in NONMEM using a published population pharmacokinetic model. Infliximab concentrations were then predicted based on each patient's dosing history and compared with actual measured concentrations (n = 59). In addition, doses 5 to 10 mg/kg and dosing intervals every 4 to 8 weeks were simulated in each patient to examine dose-trough relationships.Results:Predicted concentrations were within ±1.0 μg/mL of actual measured concentrations for 88% of measurements. The median prediction error (ie, measure of bias) was -0.15 μg/mL (95% confidence interval -0.37 to -0.05 μg/mL) and absolute prediction error (ie, measure of precision) was 0.26 μg/mL (95% confidence interval 0.15 to 0.40 μg/mL). At standard maintenance dosing of 5 mg/kg every 8 weeks, a trough >3 μg/mL was predicted to be achieved in 32% of patients. To achieve a trough >3 μg/mL, a dosing interval ≤every 6 weeks was predicted to be required in 29% of patients.Conclusions:A published IFX population pharmacokinetic model demonstrated accurate predictive performance in a pediatric CD population. Individualized IFX dosing strategies in children with CD will be critical to consistently achieve trough concentrations associated with optimal outcomes.

Original languageEnglish
Pages (from-to)639-645
Number of pages7
JournalJournal of pediatric gastroenterology and nutrition
Issue number6
Early online date2017
Publication statusPublished - 1 Dec 2017


  • Crohn disease
  • children
  • inflammatory bowel disease
  • infliximab
  • modeling and simulation
  • pharmacokinetics

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