Importance of pharmacokinetics in the management of hemophilia

Abstract

Hemophilia A and hemophilia B are caused by congenital deficiency of factor VIII and factor IX, respectively, and may lead to recurrent, spontaneous bleeding into the muscles and joints resulting in disabling arthropathy. Effective management is available in the form of prophylactic infusions of clotting factor concentrates which have been demonstrated to prevent bleeding episodes and greatly improve the quality of life of these patients. Prophylaxis is, however, expensive. Usual dosing regimens rely on weight based calculations but dosing with an understanding of an individual's pharmacokinetic response has been demonstrated to be more effective in predicting clotting factor levels that protect against bleeding episodes. Standard pharmacokinetic studies require a prohibitive number of time sampling points but recent population or Bayesian pharmacokinetics can be used to provide an accurate estimation of an individual's pharmacokinetic response using a limited number of sampling time points. The use of population pharmacokinetics has the potential to greatly increase the use of pharmacokinetic dosing regimens and optimize the use of clotting factor concentrates in patients with hemophilia. Pediatr Blood Cancer 2012; 60: S27–S29.