Administration of DDAVP did not improve the pharmacokinetics of FVIII concentrate in a clinically significant manner
Autor: | Janneke I. Loomans, Eva Stokhuijzen, Marjolein Peters, Karin Fijnvandraat |
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Přispěvatelé: | ACS - Pulmonary hypertension & thrombosis, Graduate School, Paediatric Oncology, Paediatric Haematology, Amsterdam Reproduction & Development (AR&D) |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
desmopressin
Vasopressin congenital hereditary and neonatal diseases and abnormalities half-life biology business.industry Special Issue Article Half-life factor VIII concentrate Pharmacology Hemophilia A Placebo Recombinant factor viii Von Willebrand factor Pharmacokinetics In vivo hemic and lymphatic diseases von Willebrand Factor biology.protein medicine Desmopressin business medicine.drug |
Zdroj: | Journal of clinical and translational research, 3(Suppl 2), 351-357 Journal of Clinical and Translational Research |
ISSN: | 2382-6533 |
Popis: | 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. |
Databáze: | OpenAIRE |
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