摘要
目的 比较两种重组人凝血因子Ⅷ(FⅧ)制剂拜科奇(Kogenate?FS)与百因止(Advate?)在血友病A患者中的群体药代动力学差异,以期为血友病A患者精准个体化治疗提供理论依据.方法 以WAPPS-Hemo项目中自2015年1月至2017年12月共纳入全球41个血友病中心至少接受过1次拜科奇或百因止注射的中间型/重型血友病A患者作为研究对象.计算两种FⅧ制剂的半衰期以及FⅧ活性到达2%的时间(TAT2%),并进一步分析不同年龄层和不同注射剂量下两种药物的药代动力学差异.结果 ①拜科奇组117例,平均年龄为(27.6±17.7)岁;百因止组120例,平均年龄为(23.4±16.2)岁.两组患者均为男性.②拜科奇组、百因止组给药剂量分别为(31.5±13.1)IU/kg、(38.17±14.83)IU/kg,半衰期分别为(12.3±3.5)h、(10.8±2.9)h,TAT2%分别为(65.2±21.7)h、(57.0±17.9)h.③拜科奇组中≥12岁、<12岁患者的半衰期分别为(12.7±3.7)h、(11.1±2.5)h,TAT2%分别为(68.6±22.9)h、(55.8±14.6)h;百因止组中≥12岁、<12岁患者的半衰期分别为(11.4±3.1)h、(9.4±1.8)h,TAT2%分别为(61.1±18.0)h、(45.2±11.3)h.④拜科奇组中<20 IU/kg、20~29 IU/kg、30~39 IU/kg、≥40 IU/kg剂量组的半衰期分别为(13.3±4.0)h、(12.3±3.6)h、(12.2±3.5)h、(11.6±2.6)h,TAT2%分别为(61.5±21.4)h、(63.9±22.4)h、(67.0±24.3)h、(68.0±19.5)h;百因止组中<20 IU/kg、20~29 IU/kg、30~39 IU/kg、≥40 IU/kg剂量组的半衰期分别为(11.5±3.8)h、(11.4±3.7)h、(11.0±2.9)h、(10.4±2.3)h,TAT2%分别为(50.8±19.2)h、(56.7±21.0)h、(58.2±18.8)h、(58.1±15.8)h.结论 在不同年龄组和不同注射剂量组,拜科奇的药代动力学参数均优于百因止.
Objective To compare the differences in population pharmacokinetic(PK)parameters between two recombinant coagulation factorⅧ(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 FⅧactivity reaching 2%(TAT 2%)were calculated,and the differences of PK between the two drugs among different age and dose subgroups were further analyzed.Results①The 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±1
作者
华宝来
Pierre Chelle
Cindy HT Yeung
顾健
赵永强
Alfonso Iorio
Hua Baolai;Pierre Chelle;Cindy HT Yeung;Gu Jian;Zhao Yongqiang;Alfonso Iorio(Department of Hematology,School of Clinical Medicine,Yangzhou University,Yangzhou225001,China;Department of Hematology,Peking Union Medical College Hospital,Beijing100032,China;School ofPharmacy,University of Waterloo,Canada;Department of Health Research Methods,Evidence,andImpact Communications Research Laboratory,McMaster University,Canada)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2019年第8期673-677,共5页
Chinese Journal of Hematology
基金
北京市自然科学基金(7162151)
诺和诺德血友病研究基金(NNHRF).
