Pharmacokinetic Modelling of Intravenous Immunoglobulin in Children with Primary Immunodeficiencies and Secondary Antibody Deficiencies

Children with primary immunodeficiency (PID) and secondary antibody deficiency (SAD) often require immunoglobulin replacement therapy due to low plasma immunoglobulin G (IgG) levels and recurrent infections. Existing pharmacokinetic models for immunoglobulin in primary immunodeficiency patients predominantly focus on adults, with limited attention to secondary antibody deficiencies and a lesser emphasis on paediatric populations. A population pharmacokinetic analysis was conducted using NONMEM® (7.5.1) on data from 64 patients, with a median age of 4.08 years (range: 0.06–16.8 years). A two-compartment model with first-order elimination, incorporating both additive and proportional residual error, adequately described the data. Inter-individual variability was modelled on clearance, volume of distribution, and baseline IgG levels, with allometric scaling to a 70 kg body weight applied a priori. The estimated clearance was 0.308 L−1 day−1 70 kg−1 (95% CI: 0.23–0.67), and the volume of distribution was 10.96 L−1 70 kg−1 (95% CI: 5.97–15.79). Patients with SAD exhibited a lower clearance rate of 54% compared to PID patients. Dosing simulations indicated that the recommended SAD dosing regimen maintained therapeutic IgG levels in the simulated population. However, only 44.8% to 51.9% of patients with PID achieved target IgG levels with the standard regimen. Administering a loading dose would improve the probability of maintaining therapeutic IgG levels during the 4-week dosing interval. This study provides insights into immunoglobulin pharmacokinetics in paediatric PID and SAD patients, guiding optimised dosing strategies.