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
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).
Authors
- Alexandra Power‐Hays (ORCID: https://orcid.org/0000-0002-5823-0218)
- Andrea L. Conroy (ORCID: https://orcid.org/0000-0002-5328-6511)
- Kathryn McElhinney
- Charles Drago Kato (ORCID: https://orcid.org/0000-0003-3160-6657)
- Alexander A. Vinks (ORCID: https://orcid.org/0000-0003-4224-2967)
- Russell E. Ware (ORCID: https://orcid.org/0000-0001-9582-0594)
- Teresa Latham (ORCID: https://orcid.org/0000-0002-4473-5821)
- Chandy C. John (ORCID: https://orcid.org/0000-0002-1634-1411)
- Ruth Namazzi (ORCID: https://orcid.org/0000-0003-2459-6526)
- Adam Lane (ORCID: https://orcid.org/0000-0002-5522-8112)
- Robert Opika Opoka (ORCID: https://orcid.org/0000-0003-3240-2058)
- Min Dong (ORCID: https://orcid.org/0000-0002-8552-8298)
- Caroline Kazinga
- Sadat Aliwuya
Institutions
- Cincinnati Children's Hospital Medical Center (US)
- Aga Khan University Nairobi (KE)
- World Health Organization - Uganda (UG)
- DGA Partners (US)
- Indiana University School of Medicine
- Indiana University – Purdue University Indianapolis (US)
- University of Cincinnati (US)
- Makerere University (UG)
Publication Details
- Journal
- British Journal of Clinical Pharmacology
- Published
- 2025-04-13
- DOI
- https://doi.org/10.1002/bcp.70071
- Citations
- 1
- Primary Topic
- Hemoglobinopathies and Related Disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- Cincinnati Children's Hospital Medical Center
- National Heart, Lung, and Blood Institute
- National Institute of Child Health and Human Development