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

Thromb Haemost. 2021 Oct;121(10):1326-1336. doi: 10.1055/a-1376-0970. Epub 2021 Apr 14.


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 24 hours post home infusion of FVIII and then 3 hours 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Ambulatory Care
  • Australia
  • Blood Coagulation / drug effects*
  • Canada
  • Child
  • Child, Preschool
  • Clinical Protocols
  • Coagulants / administration & dosage
  • Coagulants / blood
  • Coagulants / pharmacokinetics*
  • Czech Republic
  • Drug Monitoring*
  • Factor VIII / administration & dosage
  • Factor VIII / pharmacokinetics*
  • Hemophilia A / blood
  • Hemophilia A / diagnosis
  • Hemophilia A / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Predictive Value of Tests
  • Prospective Studies
  • Young Adult


  • Coagulants
  • Factor VIII