title: The pharmacokinetic diversity of two von Willebrand factor (VWF)/ factor VIII (FVIII) concentrates in subjects with congenital von Willebrand disease. Results from a prospective, randomised crossover study.
abstract: The pharmacokinetic (PK) profiles of von Willebrand factor (VWF) /factor VIII (FVIII) concentrates are important for treatment efficacy and safety of von Willebrand disease (VWD) patients. This prospective, head-to-head, randomised crossover study compared the PK profile of a new, high purity, human plasma-derived (pd)VWF/FVIII concentrate, Wilate, with the PK profile of an intermediate purity (pd)VWF/FVIII concentrate, Humate-P, in VWD patients. Subjects with inherited VWD were randomised to a single intravenous dose (40 IU/kg VWF ristocetin cofactor activity [VWF:RCo]) of Wilate or Humate-P in Period 1, and switched to the other study drug in Period 2. Each period was preceded by a washout time of ≥ 7 days. Coagulation factor parameters were analysed at multiple time-points. Of 22 randomised subjects, 20 had evaluable PK profiles, which indicated comparability for VWF antigen and VWF:RCo between Wilate and Humate-P. The reported VWF:RCo average and terminal t1/2 of 10.4 and 15.8 hours (h), respectively, for Wilate and 9.3 h and 12.8 h for Humate-P, were not statistically different. Also, the mean VWF:RCo in vivo recoveries (Wilate 1.89, Humate-P 1.99 IU/dl per IU/kg) were similar between the two replacement therapies. Wilate showed parallel decay curves for VWF:RCo and FVIII clotting activity (FVIII:C) over time, while FVIII:C of Humate-P displayed a plateau between 0 and 12-24 h. This study demonstrated bioequivalent PK properties for VWF between Wilate and Humate-P. The PK profile of Wilate, combined with the 1:1 VWF/FVIII ratio, theoretically should facilitate dosing and laboratory monitoring of VWF replacement to prevent bleeding in individuals with VWD.
authors: Hemophilia and Thrombophilia Comprehensive Treatment Center, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3800 Reservoir Road NW, Washington, DC 20007, USA. kesslerc@gunet.georgetown.edu
authors: Craig M
authors: CM
authors: Kessler
authors: Ken
authors: K
authors: Friedman
authors: Bruce A
authors: BA
authors: Schwartz
authors: Joan C
authors: JC
authors: Gill
authors: Jerry S
authors: JS
authors: Powell
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D005169:Factor VIII / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055503:Protein Multimerization; D013810:Therapeutic Equivalency; D055815:Young Adult; D014842:von Willebrand Diseases / Q000097:blood* / Q000188:drug therapy*; D014841:von Willebrand Factor / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII