European Journal of Pharmaceutical Sciences 37 (2009) 272–278 Contents lists available at ScienceDirect European Journal of Pharmaceutical Sciences journal homepage: www.elsevier.com/locate/ejps Pharmacokinetics of a new 10% intravenous immunoglobulin in patients receiving replacement therapy for primary immunodeficiency Richard L. Wasserman a,∗ , Joseph A. Church b , Hans H. Peter c , John W. Sleasman d , Isaac Melamed e , Mark R. Stein f , Johann Bichler g , for the IgPro10 in PID Study group 1 a Pediatric Allergy/Immunology Associates, Dallas, TX, USA b Childrens Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA c Division of Rheumatology and Clinical Immunology, University Hospital Freiburg, Freiburg, Germany d University of South Florida, All Children’s Hospital, St Petersburg, FL, USA e 1st Allergy and Asthma Center, Thornton, CO, USA f Allergy Associates of the Palm Beaches, North Palm Beach, FL, USA g CSL Behring, Bern, Switzerland article info Article history: Received 8 December 2008 Received in revised form 13 February 2009 Accepted 21 February 2009 Available online 6 March 2009 Keywords: Immunodeficiency Intravenous immunoglobulin IVIG abstract Intravenous immunoglobulin (IVIg) is used in treating immunodeficiencies and autoimmune or inflam- matory 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 ≥4 months (median dose of 444 mg/kg, at 3- or 4-week intervals). Median total IgG serum concentrations increased from 10.2 g/l pre-infusion to 23.2 g/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. Adminis- tration of IgPro10 at 3- or 4-week intervals achieved sufficient plasma concentrations of total IgG, IgG subclasses and antibodies specific to important pathogens. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Immunoglobulin therapy has been used in the treatment of many conditions, including primary immunodeficiency (PID; Orange et al., 2006). Over 100 types of PID have been described, a subset of which are characterised by antibody deficiencies that leave patients vulnerable to serious, frequent infections unless they receive regular immunoglobulin replacement therapy. As early as the 1950s, intramuscular delivery of immunoglobulins was found to have some benefit, although efficacy was limited by the quan- ∗ Corresponding author at: Pediatric Allergy/Immunology Associates, PA, 7777 Forest Lane, Suite B-332, Dallas, TX 75230, USA. Tel.: +1 972 566 7788; fax: +1 972 566 8837. E-mail address: richwasserman pdai@yahoo.com (R.L. Wasserman). 1 See Appendix A. tity of material that could be delivered via this route (Berger and Pinciaro, 2004). Intravenous immunoglobulin (IVIg) formula- tions, available since the 1980s, represent a significant advantage for these patients as they have been demonstrated to be safe and effective in decreasing the risk of infections (Ammann et al., 1982; Buckley and Schiff, 1991; Cunningham-Rundles et al., 1984). Available IVIg preparations differ in their formulation, impact- ing on storage requirements, and manufacturing processes. The latter can cause subtle changes in the IgG molecule, altering the product’s pharmacokinetic behaviour. Therefore, the pharmacoki- netic profile of each new preparation needs to be evaluated. The biologic half-life of exogenously administered IVIg is of particu- lar importance in order to tailor effective dosing regimens with sustained minimum antibody concentrations between doses. The pharmacokinetic characteristics of individual IgG subclasses (i.e., IgG 1 , IgG 2 , IgG 3 , and IgG 4 ) are also critical, as antibodies to specific 0928-0987/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ejps.2009.02.014