title: Pharmacokinetic modeling and simulation of biweekly subcutaneous immunoglobulin dosing in primary immunodeficiency.
abstract: Replacement therapy with immunoglobulin G (IgG) given as intravenous or subcutaneous (SC) infusions is the standard treatment for patients with primary immunodeficiency. Due to the life-long need for replacement, increased flexibility in the administration and dosage regimens would improve patients' quality of life. A population pharmacokinetic model that can predict plasma IgG concentrations for various routes, dosage regimens, and patient groups is a valuable tool to improve patient therapy. Such a model was developed based on IgG concentrations from 151 unique adult and pediatric patients who participated in 4 clinical trials of intravenous and SC IgG replacement therapy. Simulations predicted that the same total IgG dose, delivered SC, either in 1 biweekly dose (once every 2 weeks), or in 2 weekly doses, results in IgG peak and trough concentrations that remain within ± 10% of each other throughout the 14-day period. The developed population pharmacokinetic model predicted that biweekly SC Hizentra dosing offers a viable alternative to weekly SC therapy, allowing more flexible and optimized dosage regimens for patients with primary immunodeficiency.
authors.affiliation: Senior Research Fellow, Centre for Medicine Use and Safety, Monash University, Parkville, Australia.
authors.forename: Cornelia B
authors.initials: CB
authors.lastname: Landersdorfer
authors.forename: Martin
authors.initials: M
authors.lastname: Bexon
authors.forename: Jonathan
authors.initials: J
authors.lastname: Edelman
authors.forename: Mikhail
authors.initials: M
authors.lastname: Rojavin
authors.forename: Carl M J
authors.initials: CM
authors.lastname: Kirkpatrick
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Lu
authors.forename: Marc
authors.initials: M
authors.lastname: Pfister
authors.forename: Jagdev
authors.initials: J
authors.lastname: Sidhu
mesh_terms: D019540:Area Under Curve; D017326:Clinical Trials, Phase III as Topic; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000378:metabolism*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008657:Metabolic Clearance Rate; D008954:Models, Biological
chemical_list: C558471:Hizentra; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous