A Practical, One-Clinic Visit Protocol for Pharmacokinetic Profile Generation with the ADVATE myPKFiT Dosing Tool in Severe Hemophilia A Subjects

Authors	BLANCHETTE V. S. ZUNINO L. GRASSMANN V. BARNES C. CARCAO M. D. CURTIN J. JACKSON S. KHOO L. KOMRSKA Vladimir LILLICRAP D. MORFINI M. ROMANOVÁ Gabriela STEPHENS D. ZAPOTOCKA Ester RAND M. L. BLATNÝ Jan
Year of publication	2021
Type	Article in Periodical
Magazine / Source	THROMBOSIS AND HAEMOSTASIS
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1376-0970
Doi	http://dx.doi.org/10.1055/a-1376-0970
Keywords	factor VIII; hemophilia A; pharmacokinetic; observational study; population PK
Description	Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72-hour washout and 5 to 11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout, 6-sampling time point PPK protocol with a no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol in persons with severe hemophilia A (SHA) receiving ADVATE. A total of 39 inhibitor-negative males with SHA (factor VIII activity [FVIII:C]<2%) were enrolled in a prospective sequential design PK study. Participants completed a washout, 6-sampling time point PPK protocol as well as a no-washout, reverse 2-sampling time point protocol, with samples taken during a single 3-hour clinic visit 24hours post home infusion of FVIII and then 3hours post infusion in clinic. FVIII:C levels were analyzed by one-stage and chromogenic assays; blood group and von Willebrand factor antigen (VWF:Ag) were determined; and PK parameters were analyzed using the ADVATE myPKFiT dosing tool. There was moderate to almost perfect agreement for the PK parameters obtained with the 2- and the 6- point PPK protocols using a one-stage FVIII:C assay and a substantial to almost perfect agreement using a chromogenic FVIII:C assay. Significant associations between specific PK parameters and blood group and VWF:Ag were observed. The no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol can be used in the routine clinical setting since it demonstrates sufficient accuracy compared with the more demanding and less practical washout, 6-sampling time point PPK protocol in persons with SHA receiving ADVATE.