Population pharmacokinetics of two recombinant human coagulation factor Ⅷ preparations in patients with hemophilia A.
10.3760/cma.j.issn.0253-2727.2019.08.009
- Author:
Bao Lai HUA
1
,
2
;
Pierre CHELLE
3
;
Cindy HT YEUNG
4
;
Jian GU
5
;
Yong Qiang ZHAO
6
;
Alfonso IORIO
4
Author Information
1. Department of Hematology, School of Clinical Medicine, Yangzhou University, Yangzhou 225001, China
2. Department of Hematology, Peking Union Medical College Hospital, Beijing 100032, China.
3. School of Pharmacy, University of Waterloo, Canada.
4. Department of Health Research Methods, Evidence, and Impact Communications Research Laboratory, McMaster University, Canada.
5. Department of Hematology, School of Clinical Medicine, Yangzhou University, Yangzhou 225001, China.
6. Department of Hematology, Peking Union Medical College Hospital, Beijing 100032, China.
- Publication Type:Journal Article
- Keywords:
Factor Ⅷ;
Hemophilia A;
Pharmacokinetics
- MeSH:
Adolescent;
Adult;
Blood Coagulation Tests;
Child;
Factor VIII/therapeutic use*;
Hemophilia A/drug therapy*;
Humans;
Male;
Recombinant Proteins;
Young Adult
- From:
Chinese Journal of Hematology
2019;40(8):673-677
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To compare the differences in population pharmacokinetic (PK) parameters between two recombinant coagulation factor Ⅷ (FⅧ) preparations, Kogenate FS and Advate, in patients with hemophilia A, and to provide the theoretical basis of precise individualized treatment for those patients. Methods: Patients with moderate or severe hemophilia A who had at least one injection of Kogenate FS or Advate at 41 international hemophilia centers were enrolled as subjects from the WAPPS-Hemo project since January 2015 to December 2017. The half-lives of the two drugs and the time of FⅧ activity reaching 2% (TAT 2%) were calculated, and the differences of PK between the two drugs among different age and dose subgroups were further analyzed. Results: ①The mean age of patients in the Kogenate FS (n=117) and Advate groups (n=120) were (27.6±17.7) and (23.4±16.2) years old, respectively. All patients in the two groups were males. ②The administration doses in the Kogenate FS and Advate groups were (31.5±13.1) IU/kg and (38.17±14.83) IU/kg, respectively; the half-lives of the two drugs were (12.3±3.5) h and (10.8±2.9) h, respectively; and the TAT 2% were (65.2±21.7) h and (57.0±17.9) h, respectively. ③In the Kogenate FS group, the drug half-lives in patients aged ≥12 and <12 years old were (12.7±3.7) h and (11.1±2.5) h, respectively; the TAT 2% were (68.6±22.9) h and (55.8±14.6) h, respectively. In the Advate group, the drug half-lives in patients aged ≥12 and <12 years old were (11.4±3.1) h and (9.4±1.8) h, respectively; and the TAT 2% were (61.1±18.0) h and (45.2±11.3) h, respectively. ④In the Kogenate FS group, the drug half-lives in <20 IU/kg, (20-29) IU/kg, (30-39) IU/kg and ≥40 IU/kg groups were (13.3±4.0) h, (12.3±3.6) h, (12.2±3.5) h and (11.6±2.6) h, respectively; and the TAT 2% were (61.5±21.4) h, (63.9±22.4) h, (67.0±24.3) h and (68.0±19.5) h, respectively. In the Advate group, the drug half-lives in <20 IU/kg, (20-29) IU/kg, (30-39) IU/kg and <40 IU/kg groups were (11.5±3.8) h, (11.4±3.7) h, (11.0±2.9) h and (10.4±2.3) h, respectively; and the TAT 2% were (50.8±19.2) h, (56.7±21.0) h, (58.2±18.8) h and (58.1±15.8) h, respectively. Conclusion: The PK parameters of Kogenate FS are superior to those of Advate among different age and dose subgroups.
