Pharmacokinetics and safety of subcutaneous immune globulin (human), 10% caprylate/chromatography purified in patients with primary immunodeficiency disease

Clin Exp Immunol. 2010 Sep;161(3):518-26. doi: 10.1111/j.1365-2249.2010.04195.x.

Abstract

Subcutaneous administration of intravenous immunoglobulin G (IgG) preparations provides an additional level of patient convenience and more options for patients with poor venous access or a history of intravenous IgG reactions. An open-label, pharmacokinetic trial (n = 32) determined the non-inferiority of the subcutaneous versus intravenous route of 10% caprylate/chromatography purified human immune globulin intravenous (IGIV-C; Gamunex®) administration by comparing the steady-state area under the concentration-versus-time curve (AUC) of total plasma IgG in patients with primary immunodeficiency disease. Patients on stable IGIV-C received two intravenous infusions (administered 3 or 4 weeks apart). Seven to 10 days after the second intravenous infusion, all patients switched to a weekly infusion of subcutaneous IGIV-C, with the dose equal to 137% of the previous weekly equivalent intravenous dose, for up to 24 weeks. Samples for pharmacokinetic analysis were collected during steady state for intravenous and subcutaneous IGIV-C treatments. The AUC(0-) τ geometric least-squares mean ratio was 0·89 (90% confidence interval, 0·86-0·92) and met the criteria for non-inferiority. The overall mean steady-state trough concentration of plasma total IgG with subcutaneous IGIV-C was 11·4 mg/ml, 18·8% higher than intravenous IGIV-C (9·6 mg/ml). Subcutaneous IGIV-C was safe and well tolerated. Subcutaneous IGIV-C infusion-site reactions were generally mild/moderate and the incidence decreased over time. No serious bacterial infections were reported. Weekly subcutaneous IGIV-C infusion using 137% of the weekly equivalent intravenous immunoglobulin dose provides an AUC comparable to intravenous administration, thus allowing patients to maintain the same IgG preparation/formulation if switching between intravenous and subcutaneous infusions.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Area Under Curve
  • Diarrhea / chemically induced
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Humans
  • Immunoglobulin G / blood*
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunoglobulins, Intravenous / adverse effects
  • Immunoglobulins, Intravenous / pharmacokinetics*
  • Immunologic Deficiency Syndromes / drug therapy*
  • Immunologic Deficiency Syndromes / metabolism
  • Immunologic Deficiency Syndromes / pathology
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacokinetics
  • Immunologic Factors / therapeutic use
  • Infusions, Intravenous
  • Infusions, Subcutaneous
  • Metabolic Clearance Rate
  • Middle Aged
  • Respiratory Tract Infections / chemically induced
  • Sinusitis / chemically induced
  • Treatment Outcome
  • Young Adult

Substances

  • Immunoglobulin G
  • Immunoglobulins, Intravenous
  • Immunologic Factors