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Clinical Pharmacokinetics

Erschienen in:

01.11.2001 | Review Articles

Pharmacokinetics of Coagulation Factors

Clinical Relevance for Patients with Haemophilia

verfasst von: Dr Sven Björkman, Erik Berntorp

Erschienen in: Clinical Pharmacokinetics | Ausgabe 11/2001

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Abstract

Haemophilia is a recessively inherited coagulation disorder, in which an X-chromosome mutation causes a deficiency of either coagulation factor VIII (FVIII) in haemophilia A, or factor IX (FIX) in haemophilia B. Intravenous administration of FVIII or FIX can be used to control a bleeding episode, to provide haemostasis during surgery or for long term prophylaxis of bleeding. In special cases, activated factor VII (FVIIa) may be used instead of FVIII or FIX. The aim of this work is to review the pharmacokinetics of FVIII, FIX and FVIIa and to give an outline of the use of pharmacokinetics to optimise the treatment of patients with haemophilia.

The pharmacokinetics of FVIII are well characterised. The systemic clearance (CL) of FVIII is largely determined by the plasma level of von Willebrand factor (vWF), which protects FVIII from degradation. Typical average CL in patients with normal vWF levels is 3 ml/h/kg, with an apparent volume of distribution at steady state (V_ss) that slightly exceeds the plasma volume of the patient, and the average elimination half-life (t 1/2) is around 14 hours. There are still some discrepancies in the literature on the pharmacokinetics of FIX. The average CL of plasma-derived FIX seems to be 4 ml/h/kg, the V_ss is 3 to 4 times the plasma volume and the elimination t 1/2 often exceeds 30 hours. FVIIa has a much higher CL (average of 33 ml/h/kg), and a short terminal t 1/2 (at 2 to 3 hours). The V_ss is 2 to 3 times the plasma volume.

Since the therapeutic levels of coagulation factors are well defined in most clinical situations, applied pharmacokinetics is an excellent tool to optimise therapy. Individual tailoring of administration in prophylaxis has been shown to considerably increase the cost effectiveness of the treatment. Dosage regimens for the treatment of bleeding episodes or for haemostasis during surgery are also designed using pharmacokinetic data, and the advantages of using a constant infusion instead of repeated bolus doses have been explored. The influence of antibodies (inhibitors) on the pharmacokinetics of FVIII and FIX is in part understood, and the doses of coagulation factor needed to treat a patient can tentatively be calculated from the antibody titre.

In conclusion, therapeutic monitoring of coagulation factor levels and the use of clinical pharmacokinetics to aid therapy are well established in the treatment of patients with haemophilia.

The use of tradenames in this article is for product identification only and does not imply endorsement.

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Titel: Pharmacokinetics of Coagulation Factors
Clinical Relevance for Patients with Haemophilia
verfasst von: Dr Sven Björkman
Erik Berntorp
Publikationsdatum: 01.11.2001
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 11/2001
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200140110-00003

Springer Medizin

Abstract

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