Administration of DDAVP did not improve the pharmacokinetics ofFVIII concentrate in a clinically significant manner  

作　　者：Janneke I.Loomans Eva Stokhuijzen Marjolein Peters Karin Fijnvandraat 

机构地区：[1]Emma Children’s Hospital,Department of Pediatric Hematology,Academic Medical Center,University of Amsterdam,Amsterdam,the Netherlands [2]Department of Plasma Proteins,Sanquin Research,Amsterdam,the Netherlands

出　　处：《Journal of Clinical & Translational Research》2017年第4期8-14,共7页临床和转化研究

摘　　要：Background:The half-life and mean residence time(MRT)of infused recombinant factor VIII(FVIII)concentrate are associated with pre-infusion levels of von Willebrand factor(VWF)in severely affected hemophilia A patients.It is currently unknown if individual FVIII concentrate half-life and MRT can be extended by increasing endogenous VWF levels.Aim:Our aim was to evaluate the effect of a 1-deamino-8-D-arginine vasopressin(DDAVP)-induced rise in VWF concentration on the pharmacokinetics of infused FVIII in hemophilia A patients.Methods:Four adult hemophilia A patients participated in this cross-over,placebo-controlled study.Each patient received either intravenous DDAVP or placebo,one hour prior to administration of 50 IU/kg plasma-derived immune-affinity purified FVIII concentrate.Results:The combined administration of DDAVP and FVIII concentrate was well tolerated.The levels of VWF Antigen(Ag)doubled after DDAVP,whereas they remained stable after placebo infusion.This rise in VWF Ag resulted in a slight modification of the pharmacokinetic parameters of FVIII concentrate.The MRT of FVIII concentrate increased in all patients(mean from 17.6 h to 19.9 h,p<0.001,95%CI for MRT change:+4.7 to–0.3 h).However,in vivo recoveries tended to decrease following DDAVP administration.Conclusions:Collectively,these data show that administration of DDAVP did not improve the pharmacokinetics of FVIII concentrate in a clinically significant manner.Relevance for patients:Our results indicate that no clinical benefit is to be expected from the modification in FVIII pharmacokinetics resulting from DDAVP-administration prior to infusion of FVIII concentrate in hemophilia A patients.

关 键 词：HEMOPHILIA A FACTOR VIII CONCENTRATE von Willebrand FACTOR HALF-LIFE DESMOPRESSIN 

分 类 号：R55[医药卫生—血液循环系统疾病]