title: The use of pharmacokinetics in dose individualization of factor VIII in the treatment of hemophilia A.
abstract: Hemophilia A is a bleeding disorder resulting from a lack of clotting factor VIII (FVIII), and treatment typically consists of prophylactic replacement of the deficient factor. However, high between subject variability precludes the development of a 'one size fits all' dosing strategy and necessitates an individualized approach. We sought to summarize the data on the pharmacokinetics of FVIII available as a basis for the development of population pharmacokinetic models to be used in dose tailoring. Areas covered: We reviewed the pharmacokinetics of FVIII as used for the treatment of hemophilia A, with a focus on the variability observed between patients and the application of pharmacokinetic methods to dose individualization. We also explored the covariates affecting pharmacokinetic parameters, the differences between plasma-derived and recombinant FVIII and the development of extended half-life products. Expert opinion: The pharmacokinetics of factor VIII in patients with hemophilia shows a high interpatient variability, and is affected by age, weight, level of von Willebrand factor, and blood group. A population approach to estimating individual pharmacokinetics is likely to provide the most successful strategy to tailor factor concentrate dosing to the individual needs and to ensure optimal patient outcomes, while also improving the cost-effectiveness of prophylactic replacement therapy.
authors.affiliation: a School of Pharmacy, Health Sciences Campus , University of Waterloo , Waterloo , ON , Canada.
authors.forename: Alanna
authors.initials: A
authors.lastname: McEneny-King
authors.affiliation: b Health Information Research Unit , McMaster University , Hamilton , ON , Canada.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Iorio
authors.affiliation: c Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , ON , Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Foster
authors.affiliation: a School of Pharmacy, Health Sciences Campus , University of Waterloo , Waterloo , ON , Canada.
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Edginton
keywords: Dose individualization; factor VIII; haemophilia A; population pharmacokinetics