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Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (PKPD)
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2010 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 8, no 2, 269-275 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Prophylactic factor (F)VIII has been shown to reduce bleeds and arthropathy in patients with severe hemophilia A. OBJECTIVES: Assuming that the trough FVIII level is an important determinant of the efficacy of prophylaxis, this paper addresses the effect of the inter-patient variability in pharmacokinetics and different dosing regimens on trough levels. METHODS: Simulations used FVIII half-lives and in vivo recoveries (IVR), observed during clinical trials with Advate [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method], and commonly used prophylactic regimens to calculate their effect on FVIII levels during prophylaxis. RESULTS AND CONCLUSIONS: Half-life and dose frequency had a larger effect on trough FVIII and time per week with FVIII<1 IU dL(-1) than IVR and infused dose per kg. The combined effect of these parameters resulted in substantial inter-patient variability in the amount of FVIII required to sustain a desired trough level. Prophylactic regimens based on Monday, Wednesday, Friday dosing were less cost effective in maintaining a desired trough level throughout the week. Dose escalation on Friday to cover the weekend would require potentially harmful doses of FVIII in many patients, especially in young children where more than 50% would require a Friday dose of over 100 IU kg(-1) and some would require more than 400 IU kg(-1). Knowledge of individual patients' half-lives and alteration of frequency of infusions may allow the more cost-effective use of FVIII and potentially expand access to prophylaxis to a greater number of patients, especially in regions where healthcare resources are scarce.

Place, publisher, year, edition, pages
International Society on Thrombosis and Haemostasis , 2010. Vol. 8, no 2, 269-275 p.
National Category
Pharmaceutical Sciences Medical and Health Sciences
URN: urn:nbn:se:uu:diva-123015DOI: 10.1111/j.1538-7836.2009.03703.xISI: 000273687600009PubMedID: 19943875OAI: oai:DiVA.org:uu-123015DiVA: diva2:311622
Available from: 2010-04-22 Created: 2010-04-22 Last updated: 2010-12-22Bibliographically approved

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Björkman, Sven
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