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