Modeling of Body Weight Metrics for Effective and Cost-Efficient Conventional Factor VIII Dosing in Hemophilia A Prophylaxis
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Date
2017-12-01
Authors
McEneny-King, Alanna
Chelle, Pierre
Henrard, Severine
Hermans, Cedric
Iorio, Alfonso
Edginton, Andrea N.
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
The total body weight-based dosing strategy currently used in the prophylactic treatment of hemophilia A may not be appropriate for all populations. The assumptions that guide weight-based dosing are not valid in overweight and obese populations, resulting in overdosing and ineffective resource utilization. We explored different weight metrics including lean body weight, ideal body weight, and adjusted body weight to determine an alternative dosing strategy that is both safe and resource-efficient in normal and overweight/obese adult patients. Using a validated population pharmacokinetic model, we simulated a variety of dosing regimens using different doses, weight metrics, and frequencies; we also investigated the implications of assuming various levels of endogenous factor production. Ideal body weight performed the best across all of the regimens explored, maintaining safety while moderating resource consumption for overweight and obese patients.
Description
Keywords
hemophilia A, conventional factor VIII, dose metrics, obesity, population pharmacokinetics, recombinant factor-VIII, pharmacokinetics, obesity, children, therapy, boys, concentrate, overweight, management, severity