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.
- modelling and simulation
- RECOMBINANT FACTOR-VIII