Pharmacokinetic variability of factor VIII concentrates in Chinese pediatric patients with moderate or severe hemophilia A

• 作者: Chen Zhenping Huang Kun Li Gang Zhen Yingzi Wu Xinyi Ai Di Liu Guoqing Li Zekun Alfonso Iorio Wu Runhui
• 来源期刊: 儿科学研究（英文）
• 关键词: Hemophilia A Pharmacokinetics Pediatric patients FVIII concentrates
• 年，卷（期）: 2021,（1）
• 所属期刊栏目: Original Article
• 页码范围: 38-45
• 页数: 8页
• 语种: 中文
• DOI: 10.1002/ped4.12252

摘要

Importance::The use of factor VIII (FVIII) concentrates under pharmacokinetic (PK) guidance has become the main approach for treatment of hemophilia. However, limited PK research has been conducted in Chinese pediatric patients.Objective::To investigate the PK parameters of various FVIII concentrates in Chinese pediatric patients.Methods::Seventy-nine patients were enrolled (28 treated with Kogenate FS ?, 23 treated with Advate ?, and 28 treated with GreenMono?). All enrolled patients participated in single-dose PK analysis after at least a 3-day washout period. Blood samples were collected predose, as well as at 1 h, 9 h, 24 h, and 48 h after infusion; FVIII levels were measured using a one-stage clotting assay. von Willebrand Factor Antigen (VWF:Ag) levels and blood types were also determined. PK parameters were evaluated by WAPPS-Hemo. Results::Mean values of terminal elimination half-life time (t 1/2) for the Kogenate FS ?, Advate ?, and GreenMono? FVIII groups were 12.24 h, 10.18 h, and 9.62 h; median clearance values were 4.16, 6.23, and 5.11 mL·kg -1·h -1; and median in vivo recovery values were 1.97, 1.55, and 1.61 IU/dL per IU/kg. Longer t 1/2, higher in vivo recovery, and lower clearance were observed in patients with higher VWF:Ag level who were treated with recombinant concentrates. Interpretation::Chinese pediatric patients with hemophilia had FVIII PK characteristics similar to those previously observed in non-Chinese children, including large variation among individuals. VWF:Ag level and FVIII brand were associated with differences in FVIII PK. Thus, PK-guided dosing should be used to optimize individualized therapy in Chinese children.