Pharmacokinetic modeling and simulation of subcutaneous and intravenous IgG dosing in patients with primary immunodeficiency diseases

Abstract

A population pharmacokinetic (PK) model for comparing the PK of subcutaneously administered immunoglobulin G (IgG) replacement therapy (SCIG) with Gamunex-C 10% or SCIG 20% formulations in patients with primary immunodeficiency diseases was developed using data from 3 clinical trials (N = 95, 69.5% adults, 30.5% <18 years) of intravenous IG (IVIG) 10% and SCIG 10% or SCIG 20%. Serum IgG exposure following switches from IVIG 10% every 3 or 4 weeks to biweekly SCIG 20% (dose adjustment factor 1.0 or 1.37) and from weekly SCIG 20% to biweekly SCIG 20% or SCIG 20% 2-7 times/week was simulated. The PK of IVIG 10% and SCIG 20% were adequately described by a 2-compartment model with first-order absorption rate constant of exogenous IgG from an SC depot compartment into the central compartment and first-order elimination from the central compartment. Switching from IVIG 10% every 4 weeks to biweekly SCIG 20% produced similar serum IgG exposure, with lower peak and higher trough serum IgG concentrations. Switching from IVIG 10% every 3 or 4 weeks to weekly and biweekly SCIG 20% yielded comparable IgG exposure and clinically effective trough IgG concentrations.

Keywords: Exposure; Immunoglobulin G replacement therapy; Intravenous; Population pharmacokinetics; Subcutaneous.