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

Objectives: The pharmacokinetics of infliximab are highly variable in children with Crohn's 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 infliximab in children with CD. Methods: Within a cohort of 34 children with CD who had infliximab trough concentrations measured, the pharmacokinetics of each patient was estimated in NONMEM(R) using a published population pharmacokinetic model. Infliximab concentrations were then predicted based on each patient's dosing history and compared to actual measured concentrations (n = 59). In addition, doses 5-10 mg/kg and dosing intervals every 4-8 weeks were simulated in each patient to examine dose-trough relationships. Results: Predicted concentrations were within +/- 1.0 [mu]g/ml of actual measured concentrations for 88% of measurements. The median prediction error (i.e. measure of bias) was -0.15 [mu]g/ml (95%CI: -0.37 to -0.05 [mu]g/ml) and absolute prediction error (i.e. measure of precision) was 0.26 [mu]g/ml (95%CI: 0.15 to 0.40 [mu]g/ml). At standard maintenance dosing of 5 mg/kg every 8 weeks, a trough >3 [mu]g/ml was predicted to be achieved in 32% of patients. To achieve a trough >3 [mu]g/ml, a dosing interval

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