Pharmacokinetics of a new 10% intravenous immunoglobulin in patients receiving replacement therapy for primary immunodeficiency

Abstract

Intravenous immunoglobulin (IVIg) is used in treating immunodeficiencies and autoimmune or inflammatory disorders. As manufacturing processes and storage can alter IgG molecules, pharmacokinetic assessments are important for new preparations. Thus, we studied pharmacokinetics of IgPro10, a new 10% liquid IVIg product stabilised with l-proline, in patients with common variable immunodeficiency (CVID) and X-linked agammaglobulinaemia (XLA). Patients received IgPro10 for >or=4 months (median dose of 444mg/kg, at 3- or 4-week intervals). Median total IgG serum concentrations increased from 10.2g/l pre-infusion to 23.2g/l at infusion end. Serum IgG concentrations decreased in a biphasic manner; median terminal half-life was 36.6 days. Median half-lives were 33.2 for IgG(1), 36.3 for IgG(2), 25.9 for IgG(3) and 36.4 days for IgG(4). Specific antibody concentrations (anti-CMV, anti-Hemophilus influenzae type B, anti-tetanus toxoid and anti-Streptococcus pneumoniae) decreased with median half-lives of 22.3-30.5 days. IgPro10 pharmacokinetics were similar in patients with CVID and XLA, although patients with CVID showed higher levels of anti-tetanus and anti-S. pneumoniae antibodies than patients with XLA, suggesting residual specific antibody production. IgPro10 pharmacokinetics fulfilled expectations for and were similar to intact IgG products. Administration of IgPro10 at 3- or 4-week intervals achieved sufficient plasma concentrations of total IgG, IgG subclasses and antibodies specific to important pathogens.