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Publications

Clinical Trial, Phase I Journal Article Ppublish

PubMed: 40441700 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.

Br J Clin Pharmacol 91(6):1865-1872

Authors: Alexandra Power-Hays, Ruth Namazzi, Min Dong, Caroline Kazinga, Charles Kato, Sadat Aliwuya, Kathryn McElhinney, Andrea L Conroy, Adam Lane, Chandy John, Alexander A Vinks, Teresa Latham, Robert O Opoka, Russell E Ware

Affiliations

  • Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
  • Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
  • Department of Paediatrics and Child Health, Makerere School of Medicine, Kampala, Uganda.
  • Global Health Uganda, Kampala, Uganda.
  • Division of Pediatric Infectious Disease, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • NDA Partners, Washington, DC, USA.
  • Department of Paediatrics, Aga Khan University, Nairobi, Kenya.

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).

MeSH

Cells, Anemia, Pharmaceutical Preparations, Pharmacology, Pharmacology, Clinical, Child, Hydroxyurea, Pharmacokinetics

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