ArticleBritish journal of clinical pharmacology2016
Development of a pharmacokinetic-guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia.
Article in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease
Therapeutic Response Evaluation and Adherence Trial (TREAT): A Prospective Study of Hydroxyurea for Children With Sickle Cell Anemia
Who cites it
33 citing papers in PubMed.
- Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics-guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia.British journal of haematology · 2021Trial
- Hydroxycarbamide in children with sickle cell anaemia after first-dose vs. chronic therapy: pharmacokinetics and predictive models for drug exposure.British journal of clinical pharmacology · 2018Trial
- Population Pharmacokinetic and Exposure-Response Analyses of Prasugrel in Pediatric Patients with Sickle Cell Anemia.Clinical pharmacokinetics · 2018Trial
- Model-Informed Evaluation of Hydroxyurea Exposure During Lactation.Clinical pharmacology and therapeutics · 2026Article
- The Hydroxyurea Absorption Phenotype: A Key PK/PD Determinant in Sickle Cell Disease Treatment.Pharmaceutics · 2026Article
- Clinical Model-Informed Precision Dosing Consult Service for Accelerating Personalized Medication in Pediatric Patients.Clinical pharmacology and therapeutics · 2026Review
- Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations.Blood advances · 2026Article
- The Sickle Africa Data Coordinating Centre (SADaCC): a data science hub for interdisciplinary sickle cell disease research and training.Database : the journal of biological databases and curation · 2026Article
- The Coming of Age of Model-Informed Precision Therapeutics for Children.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Role ofLife (Basel, Switzerland) · 2025Article
- Article
- The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial.British journal of clinical pharmacology · 2025Article
- The modern use of hydroxyurea for children with sickle cell anemia.Haematologica · 2025Review
- The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial.British journal of clinical pharmacology · 2025Article
- Pharmacokinetic-Guided Hydroxyurea to Reduce Transfusions in Ugandan Children with Sickle Cell Anemia: Study Design of the Alternative Dosing And Prevention of Transfusions Trial.Acta haematologica · 2025Article
- Hydroxyurea Pharmacokinetic Evaluation in Patients with Sickle Cell Disease.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Rationale, Development, and Validation of HdxSim, a Clinical Decision Support Tool for Model-Informed Precision Dosing of Hydroxyurea for Children with Sickle Cell Anemia.Clinical pharmacology and therapeutics · 2024Article
- Efficacy, safety, and pharmacokinetics of a new, ready-to-use, liquid hydroxyurea in children with sickle cell anemia.Blood advances · 2023Article
- Effectiveness of Pharmacokinetic-Guided Hydroxyurea Dose Individualization in Patients with Sickle Cell Anemia: A Mini-Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Hydroxyurea pharmacokinetics and precision dosing in low-resource settings.Frontiers in molecular biosciences · 2023Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
aimsHydroxyurea has emerged as the primary disease-modifying therapy for patients with sickle cell anaemia (SCA). The laboratory and clinical benefits of hydroxyurea are optimal at maximum tolerated dose (MTD), but the current empirical dose escalation process often takes up to 12 months. The purpose of this study was to develop a pharmacokinetic-guided dosing strategy to reduce the time required to reach hydroxyurea MTD in children with SCA.
methodsPharmacokinetic (PK) data from the HUSTLE trial (NCT00305175) were used to develop a population PK model using non-linear mixed effects modelling (nonmem 7.2). A D-optimal sampling strategy was developed to estimate individual PK and hydroxyurea exposure (area under the concentration-time curve (AUC)). The initial AUC target was derived from HUSTLE clinical data and defined as the mean AUC at MTD.
resultsPK profiles were best described by a one compartment with Michaelis-Menten elimination and a transit absorption model. Body weight and cystatin C were identified as significant predictors of hydroxyurea clearance. The following clinically feasible sampling times are included in a new prospective protocol: pre-dose (baseline), 15-20 min, 50-60 min and 3 h after an initial 20 mg kg(-1) oral dose. The mean target AUC(0,∞) for initial dose titration was 115 mg l(-1) h.
conclusionWe developed a PK model-based individualized dosing strategy for the prospective Therapeutic Response Evaluation and Adherence Trial (TREAT, ClinicalTrials.gov NCT02286154). This approach has the potential to optimize the dose titration of hydroxyurea therapy for children with SCA, such that the clinical benefits at MTD are achieved more quickly.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.