Application of Population Pharmacokinetic Modeling for Individualized Infliximab Dosing Strategies in Crohn Disease.
J Pediatr Gastroenterol Nutr
; 65(6): 639-645, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-28471911
ABSTRACT
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 (nâ=â59). In addition, doses 5 to 10âmg/kg and dosing intervals every 4 to 8 weeks were simulated in each patient to examine dose-trough relationships.RESULTS:
Predicted concentrations were within ±1.0âµg/mL of actual measured concentrations for 88% of measurements. The median prediction error (ie, measure of bias) was -0.15âµg/mL (95% confidence interval -0.37 to -0.05âµg/mL) and absolute prediction error (ie, measure of precision) was 0.26âµg/mL (95% confidence interval 0.15 to 0.40âµg/mL). At standard maintenance dosing of 5âmg/kg every 8 weeks, a trough >3âµg/mL was predicted to be achieved in 32% of patients. To achieve a trough >3âµg/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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fármacos Gastrointestinais
/
Doença de Crohn
/
Infliximab
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Female
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Humans
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Male
Idioma:
En
Revista:
J Pediatr Gastroenterol Nutr
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá