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Aims: Use of infliximab (IFX) has improved outcomes in children with inflammatory bowel disease (IBD). However, a proportion of patients does not respond to IFX or loses response over time. Population pharmacokinetic (PopPK) modelling is a promising approach for IFX dose optimization, but with the increasing number of PopPK models in literature, model evaluation is essential. The aims of this study are: (i) to validate the predictive performance of existing IFX PopPK models using a cohort of children with IBD; and (ii) to perform a Bayesian estimation of the most suitable model to predict the next IFX concentrations. Methods: PubMed was searched for IFX PopPK models in children. Selected models were rebuilt and analysed using R. Model performance was assessed through goodness‐of‐fit‐plots, residuals against time, prediction error and prediction‐corrected visual predictive checks. The validation cohort consisted of 73 children with IBD who were treated with IFX in our centre between 2017 and 2023 (340 IFX measurements). Results: We identified 9 PopPK models. Model bias for individual predicted values ranged from −9.29% to 8.01% compared to bias for population predicted values. The model by Vande Casteele et al. demonstrated superior performance (individual predicted bias 2.13, population predicted bias −6.11); upon Bayesian estimation, it predicted induction trough levels with median error of 12.95% but had a median error of −69% predicting maintenance concentrations. Conclusion: The model by Vande Casteele et al. displayed superior performance in initial evaluations but had a high error in estimating next IFX levels and can only be used in practice to predict induction levels. [ABSTRACT FROM AUTHOR]

Introduction: Plasminogen deficiency is an ultra rare disease whose patients may develop ligneous lesions if untreated. Prophylactic replacement therapy with plasma derived plasminogen, Ryplazim, is efficient in treating lesions and could benefit from pharmacokinetic (PK) tailoring. Aim: The objectives of this study are to develop, evaluate and integrate into the WAPPS‐Hemo platform a Population PK model supporting prophylactic replacement therapy for Plasminogen deficient patients. Methods: Population PK modelling and evaluations followed the same protocol performed for factor VIII and IX concentrates. Limited sampling analysis used dosing and sampling scenarios in accordance with recommended treatment for Ryplazim. Results: The population PK model, derived from 16 participants included in previous clinical studies, was a 2‐compartment model whose variability was best described by fat‐free mass. Evaluations showed that the model described well the data and Bayesian forecasting in limited sampling environment led to acceptable precision for PK parameters relevant to plasminogen treatment. Conclusion: The model was integrated into the WAPPS‐Hemo webservice to help individualize prophylactic treatment in plasminogen deficient patients. Prospective PK data to be collected through the WAPPS‐Hemo database will be used to better understand plasminogen PK and improve patient care. [ABSTRACT FROM AUTHOR]

Current methods for therapeutic drug monitoring (TDM) have a long turnaround time as they involve collecting patients' blood samples followed by transferring the samples to medical laboratories where sample processing and analysis are performed. To enable real-time and minimally invasive TDM, a microneedle (MN) biosensor to monitor the levels of two important antibiotics, vancomycin (VAN) and gentamicin (GEN) is developed. The MN biosensor is composed of a hydrogel MN (HMN), and an aptamer-functionalized flexible (Flex) electrode, named HMN-Flex. The HMN extracts dermal interstitial fluid (ISF) and transfers it to the Flex electrode where sensing of the target antibiotics happens. The HMN-Flex performance is validated ex vivo using skin models as well as in vivo in live rat animal models. Data is leveraged from the HMN-Flex system to construct pharmacokinetic profiles for VAN and GEN and compare these profiles with conventional blood-based measurements. Additionally, to track pH and monitor patient's response during antibiotic treatment, an HMN is developed that employs a colorimetric method to detect changes in the pH, named HMN-pH assay, whose performance has been validated both in vitro and in vivo. Further, multiplexed antibiotic and pH detection is achieved by simultaneously employing the HMN-pH and HMN-Flex on live animals., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)