Phannacokinetics of Intravenous Immunoglobulin in Neonates

Abstract

Intravenous immunoglobulin (IVIG) may be a therapeutic adjunct to antibiotic treatment of neonatal infections. We examined the pharmacokinetics and safety of IVIG in human neonates. Thirty neonates with suspected sepsis were randomly assigned either to a treatment (receiving either 250, 500, or 1,000 mg/kg of IVIG plus antibiotics) or control (antibiotics alone) group. The 500 mg/kg dose produced a rise in total IgG for greater than 8 and in group B streptococcus (GBS) type-specific IgG for greater than 4-14 days. The type-specific antibody elevation varied with the amount of pathogen-specific antibody and dose of IVIG. Pharmacokinetic analysis suggests a Vdss of 42 ml/kg, Cl of 3.0 ml/kg/day, a biphasic elimination curve, and a terminal elimination half-life of 24.2 days. No toxicity was observed. These data may be valuable in determining optimal dosing schedules for IVIG in treating or preventing neonatal infections.

Prediction of Clearance of Monoclonal and Polyclonal Antibodies and Non-Antibody Proteins in Children: Application of Allometric Scaling

“…The values for observed clearance of monoclonal and polyclonal antibodies and non-antibody proteins were obtained from the literature [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ] and the predicted clearance values were compared with the observed values for each drug. In this study, there were 13 monoclonal antibodies, seven polyclonal antibodies, and nine therapeutic proteins (non-antibodies).…”

“…For two polyclonal antibodies Sandoglobulin [ 35 ] and Gamimune [ 36 ] the clearance values were calculated based on the mean concentration-time data provided by the authors. This was done because it was noted that the clearance values of these two polyclonal antibodies were absolute values rather than body weight adjusted as reported by the authors.…”

Antibody Kinetics and Response to Routine Vaccinations in Infants Born to Women Who Received an Investigational Trivalent Group B Streptococcus Polysaccharide CRM197-Conjugate Vaccine During Pregnancy

“…The half-life of GBS serotype-specific antibodies ranged between 39 and 46 days, which is in line with the half-life of other maternal transferred antibodies (47 days for pertussis [ 32 ], 40 days for hepatitis A [ 33 ], 43–45 days for influenza virus antibodies [ 34 ], and 38 days for respiratory syncytial virus [ 35 ]), and longer than the reported half-life of IgG following intravenous administration of immunoglobulin in neonates (24.2 days) [ 36 ].…”

Disruption of Endothelial Cell Homeostasis Plays a Key Role in the Early Pathogenesis of Coronary Artery Abnormalities in Kawasaki Disease

“…IVIG contains natural anti-cytokine antibodies, which neutralize the ‘overshoot’ of pro-inflammatory cytokines36, and may help to efficiently eliminate anti-endothelial antibodies that may mediate endothelial cell injury37. The cytoprotective effects of IVIG observed in HUVECs stimulated with sera from KD patients were not merely due to the high concentration of protein because the IVIG concentration used in this study was almost equivalent to the total serum IgG concentration 15 min after administration of 500–1,000 mg/kg of IVIG38. Although the subsequent cytoprotective effects of IVIG after 24 hours were not clear in this study, our results provide novel insights into the cytoprotective properties of IVIG in KD vasculitis, specifically with respect to the regulation of cell survival and death in response to vascular homeostasis.…”