Loomans Janneke I, Stokhuijzen Eva, Peters Marjolein, Fijnvandraat Karin
Emma Children's Hospital, Department of Pediatric Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands.
J Clin Transl Res. 2018 Feb 21;3(Suppl 2):351-357. eCollection 2018 Jul 30.
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. 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.
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.
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.
Collectively, these data show that administration of DDAVP did not improve the pharmacokinetics of FVIII concentrate in a clinically significant manner.
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.
在重度甲型血友病患者中，输注的重组凝血因子VIII（FVIII）浓缩物的半衰期和平均驻留时间（MRT）与血管性血友病因子（VWF）的输注前水平相关。目前尚不清楚是否可以通过提高内源性VWF水平来延长个体FVIII浓缩物的半衰期和MRT。我们的目的是评估1-去氨基-8-D-精氨酸加压素（DDAVP）诱导的VWF浓度升高对甲型血友病患者输注FVIII的药代动力学的影响。
四名成年甲型血友病患者参与了这项交叉、安慰剂对照研究。在给予50 IU/kg血浆源性免疫亲和纯化FVIII浓缩物前一小时，每位患者接受静脉注射DDAVP或安慰剂。
DDAVP和FVIII浓缩物联合给药耐受性良好。DDAVP给药后VWF抗原（Ag）水平翻倍，而安慰剂输注后保持稳定。VWF Ag的这种升高导致FVIII浓缩物的药代动力学参数略有改变。所有患者FVIII浓缩物的MRT均增加（平均从17.6小时增至19.9小时，p<0.001，MRT变化的95%CI：+4.7至-0.3小时）。然而，DDAVP给药后体内回收率趋于下降。
总体而言，这些数据表明，DDAVP给药并未以临床上有意义的方式改善FVIII浓缩物的药代动力学。
我们的结果表明，在甲型血友病患者输注FVIII浓缩物前给予DDAVP导致的FVIII药代动力学改变，预期不会带来临床益处。
