Paediatric Haematology-Oncology Division, Department of Child Health, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Haemophilia. 2022 Sep;28(5):720-725. doi: 10.1111/hae.14584. Epub 2022 May 10.
Pharmacokinetic (PK) studies of low-dose prophylaxis (LDP) of coagulation factor VIII (FVIII) in children with severe haemophilia A (SHA) are scarce.
This study aims to investigate the PK profile of children with SHA receiving LDP of FVIII.
Paediatric patients receiving FVIII infusions (10 IU/kg twice weekly) were included. PK profiles were estimated using the Web Accessible Population Pharmacokinetic Service for Haemophilia (WAPPS-Haemo). The primary outcomes were the terminal half-life (t ), concentration-time profile, and time to reach an FVIII level of < 1%. The secondary outcome was the suggested dosing interval of FVIII prophylaxis based on the individual PK profile.
Twenty-five patients were recruited; their mean age was 12.3 ± 3.0 years. The t differed among patients receiving LDP of FVIII twice weekly, with a median of t was 14.8 h (IQR 12.6-16). The median time to reach an FVIII level of < 1% was 73.8 h (IQR 58.8-80.3). Most patients could maintain a trough level of FVIII > 1% longer than 48 h. At 72-96 h, patients needed a second dose of FVIII infusion because the FVIII level was < 1%. The suggested dosing interval of FVIII prophylaxis ranged from daily to every 96 h, depending on the individual PK profile.
Our study identified inter-individual differences in the PK parameters using LDP of FVIII twice weekly. The inter-individual results in different dosing intervals advise the timing of LDP. Estimating individual PK parameters enables the identification of the optimal prophylaxis frequency to prevent bleedings.
关于接受低剂量预防治疗（LDP）的儿童血友病 A（SHA）患者的凝血因子 VIII（FVIII）药代动力学（PK）研究较少。
本研究旨在调查接受 FVIII LDP 的 SHA 患儿的 PK 特征。
纳入接受 FVIII 输注（10 IU/kg，每周两次）的儿科患者。使用 Web 访问人群 PK 服务（WAPPS-Haemo）估算 PK 特征。主要结局是终末半衰期（t ）、浓度-时间曲线和达到 FVIII 水平<1%的时间。次要结局是基于个体 PK 特征的 FVIII 预防治疗建议给药间隔。
共招募 25 例患者，平均年龄为 12.3±3.0 岁。接受 FVIII LDP 每周两次的患者 t 不同，中位数 t 为 14.8 h（IQR 12.6-16）。达到 FVIII 水平<1%的中位时间为 73.8 h（IQR 58.8-80.3）。大多数患者的 FVIII 谷水平可维持>48 h 以上。在 72-96 h，由于 FVIII 水平<1%，患者需要第二次 FVIII 输注。FVIII 预防治疗的建议给药间隔范围为每天至每 96 h，具体取决于个体 PK 特征。
本研究使用每周两次的 FVIII LDP 确定了个体间 PK 参数的差异。不同给药间隔的个体结果建议了 LDP 的时间。估计个体 PK 参数可确定预防出血的最佳预防治疗频率。
