Pharmacokinetic Study of Coagulation Factor Ⅷ in Adults with Severe Hemophilia A
10.19746/j.cnki.issn1009-2137.2024.05.032
- VernacularTitle:成人重型血友病A患者凝血因子Ⅷ药代动力学研究
- Author:
Ying ZHANG
1
;
Zhi-Fang GUO
;
Jing-Jing WANG
;
Wen-Liang LU
;
Jin-Yu HAO
;
Xin WANG
;
Zhi-Juan PAN
;
Yan-Ru GUO
;
Xin-Lei GUO
;
Jia-Jia SUN
;
Bo JIANG
;
Zhi LI
;
Zhi-Ping GUO
Author Information
1. 北京大学第一医院太原医院(太原市中心医院)血液科,山西太原 030006
- Keywords:
severe hemophilia A;
coagulation factor Ⅷ;
adults;
pharmacokinetics;
half-life
- From:
Journal of Experimental Hematology
2024;32(5):1509-1517
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.
