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

Zhenping Chen; Kun Huang; Gang Li; Yingzi Zhen; Xinyi Wu; Ai Di; Guoqing Liu; Zekun Li; Iorio Alfonso; Runhui Wu

doi:10.1002/ped4.12252

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

Pediatr Investig. 2021 Mar 22;5(1):38-45. doi: 10.1002/ped4.12252. eCollection 2021 Mar.

Authors

Zhenping Chen¹, Kun Huang¹, Gang Li¹, Yingzi Zhen¹, Xinyi Wu¹, Ai Di¹, Guoqing Liu¹, Zekun Li¹, Iorio Alfonso², Runhui Wu¹

Affiliations

¹ Beijing Key Laboratory of Pediatric Hematology Oncology National Key Discipline of Pediatrics Ministry of Education Hematology Oncology Center Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.
² Clinical Epidemiology and Biostatistics McMaster University Hamilton ON Canada.

Abstract

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.

Keywords: FVIII concentrates; Hemophilia A; Pediatric patients; Pharmacokinetics.