title: Pharmacokinetics of subcutaneous immunoglobulin and their use in dosing of replacement therapy in patients with primary immunodeficiencies.
abstract: Bioavailability and pharmacokinetics of subcutaneous IgG (SCIG) and intravenous IgG (IVIG) differ. It is not clear if and/or how the dose should be adjusted when switching from IVIG to SCIG. Area under the curve (AUC) of serum IgG versus time and trough level ratios (TLRs) on SCIG/IVIG were evaluated as guides for adjusting the dose. The mean dose adjustments required for non-inferior AUCs with 2 different SCIG preparations were 137% (± 12%) and 153% (± 16%). However, there were wide variations between adjustments required by different subjects, and in the resulting TLRs. In contrast, combined data from multiple studies allow estimation of the ratio of IgG levels with different dose adjustments, and of the steady state serum levels with different SCIG doses. When switching a patient from IVIG to SCIG, individualizing the dosage based on measured serum IgG levels and the clinical response is preferable to using mean pharmacokinetic parameters.
authors.affiliation: Immunology Research and Development, CSL Behring, King of Prussia, PA 19406-0901, USA. mel.berger@cslbehring.com
authors.forename: Melvin
authors.initials: M
authors.lastname: Berger
authors.forename: Mikhail
authors.initials: M
authors.lastname: Rojavin
authors.forename: Peter
authors.initials: P
authors.lastname: Kiessling
authors.forename: Othmar
authors.initials: O
authors.lastname: Zenker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D015992:Body Mass Index; D001938:Brazil; D002648:Child; D005060:Europe; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use*; D007136:Immunoglobulins / Q000008:administration & dosage / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007153:Immunologic Deficiency Syndromes / Q000628:therapy*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
chemical_list: C558471:Hizentra; D007074:Immunoglobulin G; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; C510539:Vivaglobin