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

Authors: Navarro-Mora, G ; Alberti, JJ; Mondou, E; Vilardell, D; Vicente Torres, J; Ayguasanosa, J; Paez, A

Affiliations: Syntax Sci SL, ParcBit,Edif Disset A2, Palma De Mallorca 07121, Spain. Grifols Biosci Res Grp, 79 TW Alexander Dr,4201 Res Commons, Res Triangle Pk, NC 27709 USA. Grifols Biosci Res Grp, Avinguda Generalitat 152, Sant Cugat Del Valles 08174, Spain.

Publication: International Immunopharmacology ; 2022 ; 104

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 exoge-nous 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.