Power-Hays Alexandra, Namazzi Ruth, Dong Min, Kazinga Caroline, Kato Charles, Aliwuya Sadat, McElhinney Kathryn, Conroy Andrea L, Lane Adam, John Chandy, Vinks Alexander A, Latham Teresa, Opoka Robert O, Ware Russell E
Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
Br J Clin Pharmacol. 2025 Jun;91(6):1865-1872. doi: 10.1111/bcp.70071.
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).
对于镰状细胞贫血（SCA）患儿，基于药代动力学（PK）指导的羟基脲给药可优化剂量并改善治疗效果，但在大多数患病儿童生活的资源匮乏地区，其可行性尚未得到证实。替代给药与输血预防（ADAPT）是一项前瞻性试验，旨在评估输血情况以及在乌干达使用便携式高效液相色谱（HPLC）和新型PK软件程序（HdxSim）为SCA患儿确定PK指导的羟基脲最大耐受剂量（MTD）的可行性。ADAPT招募了106名参与者，100%完成了PK检测。78%的参与者生成了PK指导剂量，其中38%在方案定义的范围内。通过HPLC准确测量血清羟基脲浓度以及羟基脲降解的可能性影响了可行性。确保全球SCA患者能够获得羟基脲至关重要，改善治疗策略需要持续创新，包括PK指导给药。ADAPT已在ClinicalTrials.gov注册（NCT05662098）。
