Dataset Information

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

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.

SUBMITTER: van Moort I

PROVIDER: S-EPMC8246536 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

van Moort Iris I Preijers Tim T Hazendonk Hendrika C A M HCAM Schutgens Roger E G REG Laros-van Gorkom Britta A P BAP Nieuwenhuizen Laurens L van der Meer Felix J M FJM Fijnvandraat Karin K Leebeek Frank W G FWG Meijer Karina K Mathôt Ron A A RAA Cnossen Marjon H MH

British journal of clinical pharmacology 20201216 6

<h4>Aims</h4>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.<h4>Methods</h4>PK profiling was performed by measuring 3 FVIII levels after a standardized dose of 50 IU kg<s ...[more]

PMID: 33232535

Similar Datasets

Project description:AimCurrent enoxaparin dosing guidelines in children are based on total body weight. This is potentially inappropriate in obese children as it may overestimate the drug clearance. Current evidence suggests that obese children may require lower initial doses of enoxaparin, therefore the aim of this work was to characterise the pharmacokinetics of enoxaparin in obese children and to propose a more appropriate dosing regimen.MethodsData from 196 unique encounters of 160 children who received enoxaparin treatment doses were analysed. Enoxaparin concentration was quantified using the chromogenic anti factor Xa (anti-Xa) assay. Patients provided a total of 552 anti-Xa samples. Existing published pharmacokinetic (PK) models were fitted and evaluated against our dataset using prediction-corrected visual predictive check plots (pcVPCs). A PK model was fitted using a nonlinear mixed-effects modelling approach. The fitted model was used to evaluate the current standard dosing and identify an optimal dosing regimen for obese children.ResultsPublished models of enoxaparin pharmacokinetics in children did not capture the pharmacokinetics of enoxaparin in obese children as shown by pcVPCs. A one-compartment model with linear elimination best described the pharmacokinetics of enoxaparin. Allometrically scaled fat-free mass with an estimated exponent of 0.712 (CI 0.66-0.76) was the most influential covariate on clearance while linear fat-free mass was selected as the covariate on volume. Simulations from the model showed that fat-free mass-based dosing could achieve the target anti-Xa activity at steady state in 77.5% and 78.2% of obese and normal-weight children, respectively, compared to 65.2% and 75.5% for standard total body weight-based dosing.ConclusionsA population PK model that describes the time course of anti-Xa activity of enoxaparin was developed in a paediatric population. Based on this model, a unified dosing regimen was proposed that will potentially improve the success rate of target attainment in overweight/obese patients without the need for patient body size categorisation. Therefore, prospective validation of the proposed approach is warranted.

Dataset Information

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

Aims

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets