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Population pharmacokinetics of plasma-derived factor IX in adult patients with haemophilia B: implications for dosing in prophylaxis

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

Purpose

Knowledge of the pharmacokinetics (PK) of plasma-derived factor IX (FIX) is still inadequate, with conflicting findings on its elimination half-life and as yet no analysis of the variance in PK between and within individuals. The aim of the study was thus to characterize the PK of plasma-derived FIX, including estimates of variance between and within patients, in adult patients and to predict the variation between individuals in dose requirement to produce a target trough level during regular prophylaxis.

Methods

Plasma FIX versus time data were compiled from four published and one unpublished PK study involving a total of 26 adult patients with severe haemophilia B. The number of PK assessments per patient varied between one and eight, yielding in total 893 measured FIX levels from 80 study occasions. A population PK model was developed to describe the whole dataset. Parameter values from the model were used to calculate the dose requirement to maintain a trough level of 1% of normal FIX activity in each patient.

Results

The disposition of FIX was well described by a three-compartment PK model. The median elimination half-life was 31 h, and the variation between individuals was modest both in PK and in dose requirement during twice-weekly prophylaxis.

Conclusion

With twice weekly dosing, the need for PK-based dose tailoring of FIX in adult patients appears to be limited. However, monitoring FIX levels should be considered in children, in patients who do not respond satisfactorily to standard dosing, and if treatment is switched from plasma-derived to recombinant FIX.

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Acknowledgements

The authors wish to thank Bio Products Laboratory for making these data available, Rukhsana Shaikh-Zaidi for providing additional information whenever needed and Peter Collins for helping us to find data and to get in touch with the company, and for critical reading of the manuscript. The original researchers in the Replenine-VF clinical study were Dr. P. Collins (Cardiff), Dr. C. Raper (Hull), Dr. V. Mitchell (Leicester), Dr. D. Prangnell (Lincoln), Dr. T. Nokes (Basingstoke), Professor C.A. Lee (London) and Dr. T. Baglin (Cambridge). The authors also wish to thank Anna Folkesson, Siv Jönsson, Akash Khandelwal and Kajsa Harling for advice and technical help in various stages of the modeling.

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  1. Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-751 24, Uppsala, Sweden

    Sven Björkman & Victor Åhlén

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  1. Sven Björkman
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  2. Victor Åhlén
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Correspondence to Sven Björkman.

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Björkman, S., Åhlén, V. Population pharmacokinetics of plasma-derived factor IX in adult patients with haemophilia B: implications for dosing in prophylaxis. Eur J Clin Pharmacol 68, 969–977 (2012). https://doi.org/10.1007/s00228-012-1211-z

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  • DOI: https://doi.org/10.1007/s00228-012-1211-z

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