Population Pharmacokinetics of Plasma‑Derived Factor X Using Clotting and Chromogenic Assays: A WAPPS‑Hemo Model.

Abstract

Background: Hereditary factor X (FX) deficiency is a rare autosomal recessive bleeding disorder for which individualized pharmacokinetic (PK) assessment can support optimized prophylactic management. The WAPPS-Hemo platform enables population pharmacokinetic (PopPK) individualized PK predictions based on sparse sampling.

Aim: To develop and evaluate a PopPK model for Coagdex, a FX concentrate, using manufacturer-provided PK data for its implementation on the WAPPS-Hemo platform.

Methods: Model development followed the standard PopPK modelling approach (structural, compartmental and variance partitioning steps and goodness of fit assessments). Covariates tested were age, body weight, height, fat-free mass, sex and assay type. Predictive evaluation was performed through Visual Predictive Checks (pcVPC) and Limited Sampling Analysis (LSA). LSA strategies were evaluated using dosing and sampling scenarios consistent with recommended treatment regimens for plasma‑derived FX (pdFX) concentrate.

Results: A two-compartment model accounting for between-occasion and between-subject variability with fat-free mass and assay-type as main covariates was selected. Evaluation showed good predictive capabilities.

Conclusion: We have developed a PopPK model to support WAPPS-Hemo individualized prophylaxis in FX deficiency using sparse PK data. Prospective PK data collected through the WAPPS‑Hemo database will be used to further characterize Factor X PK and enhance patient care.