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

Autor: Frymoyer A; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA., Hoekman DR; Academic Medical Center/Emma Children's Hospital, Amsterdam, The Netherlands., Piester TL; Stanford Children's IBD Center, Division of Gastroenterology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA., de Meij TG; VU University Medical Center, Amsterdam., Hummel TZ; Medisch Spectrum Twente, Enschede, The Netherlands., Benninga MA; Academic Medical Center/Emma Children's Hospital, Amsterdam, The Netherlands., Kindermann A; Academic Medical Center/Emma Children's Hospital, Amsterdam, The Netherlands., Park KT; Stanford Children's IBD Center, Division of Gastroenterology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.
Jazyk: angličtina
Zdroj: Journal of pediatric gastroenterology and nutrition [J Pediatr Gastroenterol Nutr] 2017 Dec; Vol. 65 (6), pp. 639-645.
DOI: 10.1097/MPG.0000000000001620
Abstrakt: 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.
Databáze: MEDLINE
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