Dosing of factor VIII concentrate by ideal body weight is more accurate in overweight and obese haemophilia A patients. Issue 6 (16th December 2020)

• Record Type: Journal Article
• Authors: van Moort, Iris; Preijers, Tim; Hazendonk, Hendrika C.A.M.; Schutgens, Roger E.G.; Laros‐van Gorkom, Britta A.P.; Nieuwenhuizen, Laurens; van der Meer, Felix J.M.; Fijnvandraat, Karin; Leebeek, Frank W.G.; Meijer, Karina; Mathôt, Ron A.A.; Cnossen, Marjon H.
• Is Part Of: British journal of clinical pharmacology. Volume 87:Issue 6(2021)
• Page Start: 2602
• Page End: 2613
• Publication Date: 2020-12-16
• Subjects: haemostasis -- modelling and simulation -- obesity -- pharmacokinetics; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.14670
• Languages: English
• ISSNs: 0306-5251

Abstract

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≤0.05 IU mL −1 ) were included with median BW of 83 kg (range: 53–133) and median age of 48 years (range: 18–77). IBW best explained observed variability between patients, as IIV for CL and V1 was reduced from 45.1 to 37.6 and 26.% to 14.1%, respectively. CL, V1 and half‐life were similar for all BMI categories. The national recommended dosing schedule did not result in adequate trough levels, both in case of dosing based on BW and IBW. However, dosing based on IBW prevented unnecessary high FVIII peaks. Conclusion: IBW is the most suitable morphometric variable to explain interindividual FVIII PK variability and is more appropriate to dose overweight and obese patients.