Pharmacokinetic analysis of anti-hemophilic factor in the obese patient

Abstract

Standard dosing for individuals with hemophilia A is based on body weight such that 50 IU kg(-1) is defined as a 100% dose, or one attaining 1.00 IU mL(-1) factor VIII (FVIII) clotting activity. No guidelines exist, however, for individuals with hemophilia who are obese, body mass index (BMI) ≥ 30, who may actually be 'over'-treated based on higher in vivo recovery based on higher weight. Alternative treatment guidelines are needed for such patients. To determine FVIII pharmacokinetics we retrospectively collected data during ideal-body-weight dosing from six obese (BMI ≥ 30) hemophilia A patients cared for at the Hemophilia Center of Western PA, for prophylaxis or surgery. The pharmacokinetic data from six subjects undergoing ideal-body-weight dosing with recombinant FVIII indicate peak levels and half-life comparable to standard 50 IU kg(-1) dosing. The mean peak FVIII:C was 1.00 IU dL(-1) and the mean FVIII:C half-life was 10.14 h. IBW-dosing resulted in an average 48.9% reduction in factor use per patient over a 3-month period, for an annualized savings of $133,000 per patient. Ideal-body-weight dosing of recombinant FVIII in obese patients with hemophilia A results in comparable pharmacokinetics, including peak and half-life, with comparable hemostatic efficacy for prophylaxis and surgical treatment, at a significant reduction in factor use and cost. Future studies are needed to confirm these findings in individuals with other congenital bleeding disorders and in children.

Keywords: hemophilia; ideal body weight; obesity; pharmacokinetics; recombinant factor VIII.