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Clinical Trial
. 2025 Jun;91(6):1865-1872.
doi: 10.1111/bcp.70071.

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

Alexandra Power-Hays  1   2 , Ruth Namazzi  3   4 , Min Dong  1 , Caroline Kazinga  4 , Charles Kato  4 , Sadat Aliwuya  4 , Kathryn McElhinney  1 , Andrea L Conroy  4   5 , Adam Lane  1 , Chandy John  5 , Alexander A Vinks  2   6 , Teresa Latham  1 , Robert O Opoka  7 , Russell E Ware  1   2
Affiliations
Clinical Trial

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

Alexandra Power-Hays et al. Br J Clin Pharmacol. 2025 Jun.

Abstract

Pharmacokinetic (PK)-guided dosing of hydroxyurea for children with sickle cell anaemia (SCA) could optimize dosing and improve outcomes, but its feasibility has not been demonstrated in low-resource settings where the majority of affected children live. Alternative Dosing And Prevention of Transfusions (ADAPT) is a prospective trial evaluating blood transfusions and the feasibility of determining PK-guided, hydroxyurea maximum tolerated doses (MTD) for children with SCA in Uganda, using portable high-performance liquid chromatography (HPLC) and a novel PK software programme (HdxSim). ADAPT enrolled 106 participants, and 100% completed PK testing. PK-guided doses were generated for 78%, of which 38% were within the protocol-defined range. Accurately, measuring serum hydroxyurea concentrations via HPLC and the potential for hydroxyurea degradation impacted the feasibility. Ensuring that people with SCA globally have access to hydroxyurea is imperative, and improving treatment strategies requires ongoing innovation including PK-guided dosing. ADAPT is registered at ClinicalTrials.gov (NCT05662098).

Keywords: HPLC < drug analysis; clinical pharmacology; haematology; paediatrics; pharmacokinetics.

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Conflict of interest statement

APH and REW were formerly on a Health Equity Advisory board for Novo Nordisk, which does not make hydroxyurea. REW serves as a Medical Advisor to Nova Laboratories, Theravia, and Merck Pharmaceuticals, and serves on a Data Safety Monitoring Board for clinical trials sponsored by Novartis and Vaxart. AAV works at NDA Partners. The other authors have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
(A) Hydroxyurea concentrations for ADAPT were determined via a portable high‐performance liquid chromatography machine (HPLC, SmartLife) capable of performing haemoglobin electrophoresis testing or determining hydroxyurea concentration depending on column and mobile phases. Figure 1B. Hydroxyurea pharmacokinetic (PK)‐guided doses were determined via a clinical decision support tool for model‐informed precision dosing (HdxSim) for children with sickle cell anaemia.
FIGURE 2
FIGURE 2
Hydroxyurea pharmacokinetic feasibility chart for the ADAPT cohort.
See this image and copyright information in PMC

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References

    1. Ware RE, de Montalembert M, Tshilolo L, Abboud MR. Sickle cell disease. Lancet. 2017;390(10091):311‐323. doi:10.1016/S0140-6736(17)30193-9 - DOI - PubMed
    1. Thomson AM, McHugh TA, Oron AP, et al. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the global burden of disease study 2021. Lancet Haematol. 2023;3026(23):e585‐e599. doi:10.1016/S2352-3026(23)00118-7 - DOI - PMC - PubMed
    1. Ware RE. Is sickle cell anemia a neglected tropical disease? PLoS Negl Trop Dis. 2013;7(5):e2120. doi:10.1371/journal.pntd.0002120 - DOI - PMC - PubMed
    1. Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Sickle cell disease in Africa: a neglected cause of early childhood mortality. Am J Prev Med. 2011;41(6 SUPPL.4):S398‐S405. doi:10.1016/j.amepre.2011.09.013 - DOI - PMC - PubMed
    1. World Health Organization . Sickle Cell Anemia. In: WHA59.20: Sickle Cell Anemia. 2006. https://apps.who.int/gb/ebwha/pdf_files/WHA59/A59_R20-en.pdf

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