Pharmacokinetic dosing in prophylactic treatment of hemophilia A

Eur J Haematol. 1993 Oct;51(4):247-52. doi: 10.1111/j.1600-0609.1993.tb00638.x.

Abstract

The aim of this study was to investigate individual pharmacokinetics as a tool for dosing of factor VIII (FVIII) in severe hemophilia A. It is assumed that effective prophylaxis against bleedings is maintained if the plasma FVIII:C activity is kept above 1 U/dl, and the present study is based on this assumption. A current standard dosage regimen for FVIII is 25-40 U/kg up to three times weekly. However, there is considerable individual variation in the pharmacokinetics of FVIII:C. Individual pharmacokinetic data were used to computer-simulate plasma activity curves after repeated doses in 8 patients. Going from prophylaxis regimens of normally 2-3 infusions per week to dosing every 2 days would theoretically reduce their average FVIII consumption by 43% with maintained or increased trough levels of FVIII:C. Daily dosing would reduce their mean FVIII usage by 82%. Modified dosage regimens, infusions every 2 days, were implemented in the patients, and plasma samples were drawn to verify the pharmacokinetic models. The feasibility of the method to generally raise trough levels with a decreased consumption of FVIII was confirmed. Dosing of coagulation factors according to kinetic principles can result in more cost-effective utilization of these very expensive preparations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Computer Simulation
  • Drug Administration Schedule
  • Factor VIII / metabolism
  • Factor VIII / pharmacokinetics*
  • Factor VIII / therapeutic use
  • Hemophilia A / blood
  • Hemophilia A / therapy*
  • Hemorrhage / prevention & control*
  • Humans
  • Kinetics
  • Middle Aged
  • Time Factors

Substances

  • Factor VIII