Cross-evaluation of Pharmacokinetic-Guided Dosing Tools for Factor VIII.

BACKGROUND:  Patients with severe and moderate haemophilia A are treated prophylactically with factor VIII (FVIII) concentrate. Individualization of prophylaxis can be achieved by pharmacokinetic (PK)-guided dosing.

AIM:  In this study, the performance of three PK tools (myPKFiT, Web-Accessible Population Pharmacokinetic Service-Hemophilia [WAPPS] and NONMEM) is compared.

METHODS:  In 39 patients, with severe or moderate haemophilia A, blood samples were collected 4, 24 and 48 hours after administration of 50 IU kg-1 of recombinant FVIII (Advate [ n  = 30] or Kogenate [ n  = 9]). FVIII dose, FVIII activity and patient characteristics were entered into the three PK tools. Obtained PK parameters and dosing advises were compared.

RESULTS:  myPKFiT provided PK parameters for 24 of 30 patients receiving Advate, whereas WAPPS and NONMEM provided estimates for all patients. Half-life was different among the three methods: medians were 12.6 hours ( n  = 24), 11.2 hours ( n  = 30) and 13.0 hours ( n  = 30) for myPKFiT, WAPPS and NONMEM ( p  < 0.001), respectively. To maintain a FVIII trough level of 0.01 IU mL-1 after 48 hours, doses for myPKFiT and NONMEM were 15.1 and 11.0 IU kg-1 ( p  < 0.01, n  = 11) and for WAPPS and NONMEM were 9.0 and 8.0 IU kg-1 ( p  < 0.01, n  = 23), respectively. In nine patients receiving Kogenate, WAPPS and NONMEM produced different PK-parameter estimates; half-life was 15.0 and 12.3 hours and time to 0.05 IU mL-1 was 69.2 and 60.8 hours, respectively ( p  < 0.01, n  = 9). However, recommended doses to obtain these levels were not different.

CONCLUSION:  The three evaluated PK tools produced different PK parameters and doses for recombinant FVIII. Haematologists should be aware that recommended doses may be influenced by the choice of PK tool.