title: Pharmacokinetics and safety of subcutaneous immune globulin (human), 10% caprylate/chromatography purified in patients with primary immunodeficiency disease.
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.
authors.affiliation: DallasAllergyImmunology, Dallas, TX 75230, USA. richwasserman_pdai@yahoo.com
authors.forename: R L
authors.initials: RL
authors.lastname: Wasserman
authors.forename: A-M
authors.initials: AM
authors.lastname: Irani
authors.forename: J
authors.initials: J
authors.lastname: Tracy
authors.forename: C
authors.initials: C
authors.lastname: Tsoukas
authors.forename: D
authors.initials: D
authors.lastname: Stark
authors.forename: R
authors.initials: R
authors.lastname: Levy
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Sorrells
authors.forename: R
authors.initials: R
authors.lastname: Roberts
authors.forename: S
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007155:Immunologic Factors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007262:Infusions, Intravenous; D055104:Infusions, Subcutaneous; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000139:chemically induced; D012852:Sinusitis / Q000139:chemically induced; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors