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Pharmaceutics 2017, 9(4), 47; https://doi.org/10.3390/pharmaceutics9040047

Modeling of Body Weight Metrics for Effective and Cost-Efficient Conventional Factor VIII Dosing in Hemophilia A Prophylaxis

1
School of Pharmacy, University of Waterloo, Waterloo, ON N2L 3G1, Canada
2
Louvain Drug Research Institute, Clinical Pharmacy Research Group and Institute of Health and Society (IRSS), Université catholique de Louvain, 1348 Brussels, Belgium
3
Haemostasis and Thrombosis Unit, Division of Haematology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, 1348 Brussels, Belgium
4
Department of Health Evidence, Research Methods and Impact, McMaster University, Hamilton, ON L8S 4L8, Canada
5
Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
*
Author to whom correspondence should be addressed.
Received: 9 September 2017 / Revised: 11 October 2017 / Accepted: 12 October 2017 / Published: 17 October 2017
(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)
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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. View Full-Text
Keywords: hemophilia A; conventional factor VIII; dose metrics; obesity; population pharmacokinetics hemophilia A; conventional factor VIII; dose metrics; obesity; population pharmacokinetics
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McEneny-King, A.; Chelle, P.; Henrard, S.; Hermans, C.; Iorio, A.; Edginton, A.N. Modeling of Body Weight Metrics for Effective and Cost-Efficient Conventional Factor VIII Dosing in Hemophilia A Prophylaxis. Pharmaceutics 2017, 9, 47.

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