Dosing of factor VIII concentrate by ideal body weight is more accurate in overweight and obese haemophilia A patients

Opti-Clot Study Grp, Iris van Moort, Tim Preijers, Hendrika C. A. M. Hazendonk, Roger E. G. Schutgens, Britta A. P. Laros-van Gorkom, Laurens Nieuwenhuizen, Felix J. M. van der Meer, Karin Fijnvandraat, Frank W. G. Leebeek, Karina Meijer, Ron A. A. Mathot, Marjon H. Cnossen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Aims Under- and, especially, overdosing of replacement therapy in haemophilia A patients may be prevented by application of other morphometric variables than body weight (BW) to dose factor VIII (FVIII) concentrates. Therefore, we aimed to investigate which morphometric variables best describe interindividual variability (IIV) of FVIII concentrate pharmacokinetic (PK) parameters.

Methods PK profiling was performed by measuring 3 FVIII levels after a standardized dose of 50 IU kg(-1) FVIII concentrate. A population PK model was constructed, in which IIV for clearance (CL) and central volume of distribution (V1) was quantified. Relationships between CL, V1 and 5 morphometric variables (BW, ideal BW [IBW], lean BW, adjusted BW, and body mass index [BMI]) were evaluated in normal weight (BMI <25 kg m(-2)), overweight (BMI 25-30 kg m(-2)) and obese haemophilia A patients (BMI > 30 kg m(-2)).

Results In total, 57 haemophilia A patients (FVIII

Conclusion IBW is the most suitable morphometric variable to explain interindividual FVIII PK variability and is more appropriate to dose overweight and obese patients.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalBritish Journal of Clinical Pharmacology
DOIs
Publication statusPublished - 16-Dec-2020

Keywords

  • haemostasis
  • modelling and simulation
  • obesity
  • pharmacokinetics
  • RECOMBINANT FACTOR-VIII
  • VON-WILLEBRAND-FACTOR
  • PHARMACOKINETICS
  • CLEARANCE
  • CHILDREN
  • INDEX
  • SIZE
  • MASS
  • AGE

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