COMPARISON OF INDIVIDUAL PHARMACOKINETIC DOSING TOOLS IN PATIENTS WITH HEMOPHILIA A

Abstract

Objective: Prophylaxis treatment is recommended for the prevention of bleeding and complications in patients with hemophilia A. Personalized treatment methods are an up-to-date approach. Hemophilia treatment is suitable for optimization with pharmacokinetic (PK) methods. It has been shown that prophylaxis regulated with PK data reduces the frequency of bleeding and the cost of treatment. To determine the best prophylaxis regimen, PK dose tools using the Bayesian method have been developed. Methodology: Blood samples were obtained from 42 patients with severe hemophilia A (median age 13.4 years) with factor VIII (FVIII) inhibitor <0.6 BU/ml and no additional disease that would affect the FVIII level before the FVIII infusion, 4, 24 and 48 hours after the infusion. FVIII levels from blood samples were measured by PTT-based one-stage assay method. PK parameters obtained using WAPPS and myPKFIT programs, which are two web-accessed PK dosing tools using the Bayesian algorithm, were compared. Results: There was no significant difference between the daily dose of FVIII given in prophylaxis and the dose amount recommended by the myPKFIT program for the 1% trough, but a difference was found with the WAPPS program. While there was no significant difference between the half-lives (t1/2) and the time to 5% of plasma FVIII between the two PK tools, there were significant differences in the recommended dose amounts, clearance (CL), times up to 1% and 2% of plasma FVIII. Conclusion: As a result of cross-pair comparison between the treatment doses received by the patients and the doses recommended by the PK dosing tools, significant differences were found as well as similarities. Besides similar results, significant differences were also found among the PK parameters. Previous studies didn't compare CLs between myPKFIT and WAPPS, this is the first in our study. While no difference was found between t1/2’s, the difference between recommended doses may be due to CL difference.