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Performance of Eight Infliximab Population Pharmacokinetic Models in a Cohort of Dutch Children with Inflammatory Bowel Disease.
Bevers, Nanja C; Keizer, Ron J; Wong, Dennis R; Aliu, Arta; Pierik, Marieke J; Derijks, Luc J J; van Rheenen, Patrick F.
Affiliation
  • Bevers NC; Department of Paediatrics, Zuyderland Medical Center, Dr. H. van der Hoffplein 1, 6162 BG, Sittard-Geleen, The Netherlands. n.bevers@zuyderland.nl.
  • Keizer RJ; NUTRIM, School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. n.bevers@zuyderland.nl.
  • Wong DR; InsightRX, San Francisco, CA, USA.
  • Aliu A; Department of Clinical Pharmacy, Pharmacology and Toxicology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands.
  • Pierik MJ; Department of Gastroenterology-Hepatology and NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
  • Derijks LJJ; Department of Gastroenterology-Hepatology and NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
  • van Rheenen PF; Department of Clinical Pharmacy and Clinical Pharmacology, Máxima Medical Center, Veldhoven, The Netherlands.
Clin Pharmacokinet ; 63(4): 529-538, 2024 Apr.
Article in En | MEDLINE | ID: mdl-38488984
ABSTRACT
BACKGROUND AND

OBJECTIVE:

Efficacy of infliximab in children with inflammatory bowel disease can be enhanced when serum concentrations are measured and further dosing is adjusted to achieve and maintain a target concentration. Use of a population pharmacokinetic model may help to predict an individual's infliximab dose requirement. The aim of this study was to evaluate the predictive performance of available infliximab population pharmacokinetic models in an independent cohort of Dutch children with inflammatory bowel disease.

METHODS:

In this retrospective study, we used data of 70 children with inflammatory bowel disease (443 infliximab concentrations) to evaluate eight models that focused on infliximab pharmacokinetic models in individuals with inflammatory bowel disease, preferably aged ≤ 18 years. Predictive performance was evaluated with prior predictions (based solely on patient-specific covariates) and posterior predictions (based on covariates and infliximab trough concentrations). Model accuracy and precision were calculated with relative bias and relative root mean square error and we determined the classification accuracy at the trough concentration target of ≥ 5 mg/L.

RESULTS:

The population pharmacokinetic model by Fasanmade was identified to be most appropriate for the total dataset (relative bias before/after therapeutic drug monitoring -20.7%/11.2% and relative root mean square error before/after therapeutic drug monitoring 84.1%/51.6%), although differences between models were small and several were deemed suitable for clinical use. For the Fasanmade model, sensitivity and specificity for maximum posterior predictions for the next infliximab trough concentration to be ≥ 5 mg/L were respectively 83.5% and 80% with an area under the receiver operating characteristic curve of 0.870.

CONCLUSIONS:

In our paediatric cohort, various models provided acceptable predictive performance, with the Fasanmade model deemed most suitable for clinical use. Model-informed precision dosing can therefore be expected to help to maintain infliximab trough concentrations in the target range.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gastrointestinal Agents / Inflammatory Bowel Diseases / Drug Monitoring / Infliximab / Models, Biological Limits: Adolescent / Child / Child, preschool / Female / Humans / Male Country/Region as subject: Europa Language: En Journal: Clin Pharmacokinet Year: 2024 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gastrointestinal Agents / Inflammatory Bowel Diseases / Drug Monitoring / Infliximab / Models, Biological Limits: Adolescent / Child / Child, preschool / Female / Humans / Male Country/Region as subject: Europa Language: En Journal: Clin Pharmacokinet Year: 2024 Document type: Article