Simulation-Based Optimization of Sampling Schedules for Model-Informed Precision Dosing of Once-Daily and 4-Times-Daily Busulfan in Pediatric Patients
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Le résumé fourni par la source
BACKGROUND: Therapeutic drug monitoring (TDM) is crucial in optimizing the outcomes of hematopoietic stem cell transplantation by guiding busulfan (Bu) dosing. Limited sampling strategies show promise for efficiently adjusting drug doses. However, comprehensive assessments and optimization of sampling schedules for Bu TDM in pediatric patients are limited. We aimed to establish optimal sampling designs for model-informed precision dosing (MIPD) of once-daily (q24h) and 4-times-daily (q6h) Bu administration in pediatric patients. METHODS: Simulated data sets were used to evaluate the population pharmacokinetic model-based Bayesian estimation of the area under the concentration-time curve (AUC) for different limited sampling strategy designs. The evaluation was based on the mean prediction error for accuracy and root mean square error for precision. These findings were validated using patient-observed data. In addition, the MIPD protocol was implemented in the Tucuxi software, and its performance was assessed. RESULTS: Our Bayesian estimation approach allowed for flexible sampling times while maintaining mean prediction error within ±5% and root mean square error below 10%. Accurate and precise AUC 0-24h and cumulative AUC estimations were obtained using 2-sample and single-sample schedules for q6h and q24h dosing, respectively. TDM on 2 separate days was necessary to accurately estimate cumulative exposure, especially in patients receiving q6h Bu. Validation with observed patient data confirmed the precision of the proposed limited sampling scenarios. Implementing the MIPD protocol in Tucuxi software yielded reliable AUC estimations. CONCLUSIONS: Our study successfully established precise limited sampling protocols for MIPD of Bu in pediatric patients. Our findings underscore the importance of TDM on at least 2 occasions to accurately achieve desired Bu exposures. The developed MIPD protocol and its implementation in Tucuxi software provide a valuable tool for routine TDM in pediatric hematopoietic stem cell transplantation.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Simulation-Based Optimization of Sampling Schedules for Model-Informed Precision Dosing of Once-Daily and 4-Times-Daily Busulfan in Pediatric Patients
- Date Crossref
- 14/06/2024
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Geneva pays non établi dans la noticeUniversité ou école supérieure
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University Hospital of Geneva Division of Clinical Pharmacology and Toxicology pays non établi dans la noticeÉtablissement de santé
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Centre Hospitalier Universitaire Sainte-Justine pays non établi dans la noticeÉtablissement de santé
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Stiftung Liebenau (Germany) pays non établi dans la noticeEntreprise
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CHU Sainte-Justine Research Center Charles-Bruneau Cancer Center pays non établi dans la noticeStructure de recherche
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Université de Montréal pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Medicine Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Clinical Pharmacology Unit pays non établi dans la noticeÉtablissement de santé
University of Geneva, Division of Clinical Pharmacology and Toxicology — University Hospital of Geneva et Centre Hospitalier Universitaire Sainte-Justine, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.