Pharmacokinetic dosing in prophylactic treatment of hemophilia A.
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.
Carlsson
M
M
Hospital Pharmacy, Malmö General Hospital, Sweden.
Berntorp
E
E
Björkman
S
S
Lindvall
K
K
D000328:Adult; D000368:Aged; D003198:Computer Simulation; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006467:Hemophilia A / Q000097:blood / Q000628:therapy*; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D013997:Time Factors
D005169:Factor VIII