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In vivo recovery of factor VIII and factor IX: intra- and interindividual variance in a clinical setting
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy. (MHU)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy. (MHU)
2007 (English)In: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 13, no 1, 2-8 p.Article in journal (Refereed) Published
Abstract [en]

In vivo recovery (IVR) is traditionally used as a parameter to characterize the pharmacokinetic properties of coagulation factors. It has also been suggested that dosing of factor VIII (FVIII) and factor IX (FIX) can be adjusted according to the need of the individual patient, based on an individually determined IVR value. This approach, however, requires that the individual IVR value is more reliably representative for the patient than the mean value in the population, i.e. that there is less variance within than between the individuals. The aim of this investigation was to compare intra- and interindividual variance in IVR (as U dL−1 per U kg−1) for FVIII and plasma-derived FIX in a cohort of non-bleeding patients with haemophilia. The data were collected retrospectively from six clinical studies, yielding 297 IVR determinations in 50 patients with haemophilia A and 93 determinations in 13 patients with haemophilia B. For FVIII, the mean variance within patients exceeded the between-patient variance. Thus, an individually determined IVR value is apparently no more informative than an average, or population, value for the dosing of FVIII. There was no apparent relationship between IVR and age of the patient (1.5–67 years). For FIX, the mean variance within patients was lower than the between-patient variance, and there was a significant positive relationship between IVR and age (13–69 years). From these data, it seems probable that using an individual IVR confers little advantage in comparison to using an age-specific population mean value. Dose tailoring of coagulation factor treatment has been applied successfully after determination of the entire single-dose curve of FVIII:C or FIX:C in the patient and calculation of the relevant pharmacokinetic parameters. However, the findings presented here do not support the assumption that dosing of FVIII or FIX can be individualized on the basis of a clinically determined IVR value.

Place, publisher, year, edition, pages
2007. Vol. 13, no 1, 2-8 p.
Keyword [en]
dosing, factor VIII, factor IX, in vivo recovery, pharmacokinetics, variance
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-23493DOI: 10.1111/j.1365-2516.2006.01401.xISI: 000243982900002PubMedID: 17212717OAI: oai:DiVA.org:uu-23493DiVA: diva2:51267
Available from: 2007-01-29 Created: 2007-01-29 Last updated: 2017-12-07Bibliographically approved

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Björkman, Sven E.

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