Pharmacokinetics of total immunoglobulin G and immunoglobulin G subclasses in patients undergoing replacement therapy for primary immunodeficiency syndromes

Abstract

Background and objectives: Careful evaluation of the pharmacokinetic properties of a new immunoglobulin G (IgG) preparation is necessary to ensure that the product will not deviate significantly from existing products, in terms of pharmacological activity.

Materials and methods: A prospective, open and uncontrolled trial was performed in 16 patients with primary immunodeficiency syndromes. Patients who had been under replacement therapy with licensed preparations prior to study inclusion, received 280 +/- 60 mg/kg of a solution of IgG, ready for intravenous administration, every 3 weeks for 6 months. Trough and peak plasma levels were measured immediately before and 1 h after each infusion, respectively. Pharmacokinetic parameters were calculated for total IgG and IgG subclasses.

Results: Total IgG, IgG1, IgG2 and IgG3 declined mono-exponentially in contrast to IgG4 which showed a bi-exponential decline. Half-lives which were highly variable among patients were similar for total IgG, IgG1 and IgG2 (35.9 +/- 10.8, 36.3 +/- 9.2, and 37.1 +/- 13.9 days, respectively) and shorter for IgG3 and IgG4 (28.6 +/- 10.4 and 15.6 +/- 4.5 days, respectively).

Conclusions: The decline of IgG4 probably reflected a complex catabolic pathway specific for this subclass. As the plasma level of IgG4 is low, the decline of total IgG remained unaffected. Pharmacokinetic properties were consistent with results reported elsewhere in patients undergoing replacement therapy for primary immunodeficiency syndromes.