Pharmacokinetics of Intravenous Immunoglobulin in Neonates

Weisman, Leonard E.; Fischer, Gerald W.; Marinelli, Philip V.; Hemming, Val G.; Pierce, John R.; Golden, Stephen M.; Peck, Carl C.

doi:10.1159/000461056

Cited by 11 publications

(14 citation statements)

References 22 publications

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“…In addition, the AEs, SAEs, and clinical outcomes across study groups were not significantly different. This is also similar to previous reports of IgG safety and tolerability in neonates (35,36). This study suggests that the first use of pagibaximab in VLBW neonates at 10, 30, 60, and 90 mg/kg administered i.v.…”

Section: Discussionsupporting

confidence: 91%

“…The mean t 1/2 ranged from 19 to 25 days across the dose groups and is consistent with previous reports of IgG infusions in neonates (35,36). This is also consistent with results from a previous study of pagibaximab in healthy human adults (38), with other studies of human/mouse chimeric or full human IgG1 antibodies administered i.v.…”

Section: Discussionsupporting

confidence: 91%

“…This is also consistent with results from a previous study of pagibaximab in healthy human adults (38), with other studies of human/mouse chimeric or full human IgG1 antibodies administered i.v. in adults (4,9,22,29), and commercially available intravenous immunoglobulin in neonates (35,36). Moreover, after the second infusion of pagibaximab at 60 or 90 mg/kg, mean anti-LTA levels greater than 500 g/ml, the putative protection level for staphylococcal sepsis, were observed.…”

Section: Discussionmentioning

confidence: 99%

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Phase 1/2 Double-Blind, Placebo-Controlled, Dose Escalation, Safety, and Pharmacokinetic Study of Pagibaximab (BSYX-A110), an Antistaphylococcal Monoclonal Antibody for the Prevention of Staphylococcal Bloodstream Infections, in Very-Low-Birth-Weight Neonates

Weisman

Thackray²,

Garcia‐Prats

et al. 2009

Antimicrob Agents Chemother

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Staphylococcal sepsis is a major cause of morbidity and mortality in very-low-birth-weight (VLBW) infants.A human chimeric monoclonal antibody, pagibaximab, was developed against staphylococcal lipoteichoic acid. We evaluated the safety, tolerability, and pharmacokinetics of pagibaximab in VLBW neonates. A phase 1/2, randomized, double-blind, placebo-controlled, dose escalation study was conducted in VLBW infants (700 to 1,300 g) 3 to 7 days old. Patients received two doses 14 days apart of intravenous pagibaximab (10, 30, 60, or 90 mg/kg of body weight) or placebo in a 2:1 ratio. Blood and urine samples were obtained pre-and postinfusion for analysis of safety and pharmacokinetics, and data on adverse events were gathered. Staphylococcal organisms causing sepsis were collected and evaluated. Fifty-three patients received at least one dose of pagibaximab or placebo. The average gestational age was 27.6 weeks; the average birth weight was 1,003 g. All serious adverse events were deemed unrelated or probably not drug related. Morbidity and mortality were similar across treatment groups. No evidence of immunogenicity of pagibaximab was detected. Pagibaximab pharmacokinetics was linear. The mean clearance (CL), volume of distribution, and elimination half-life of pagibaximab were independent of dose. The serum half-life was 20.5 ؎ 6.8 days. Pagibaximab enhanced serum opsonophagocytic activity. All staphylococci causing sepsis were opsonizable by pagibaximab. Two infusions of pagibaximab, administered 2 weeks apart to high-risk neonates appeared safe and tolerable, and pharmacokinetics were linear. Evaluation of more frequent doses, at the highest doses tested, in neonates at high-risk of staphylococcal sepsis, is warranted.Very-low-birth-weight (VLBW) neonates (Ͻ1,500-g birth weight) are at high risk for late-onset (Ͼ72 h of life) hospitalacquired sepsis (13,16,17). Such infections are a major cause of morbidity, prolong time in the hospital and intensive care unit, increase the need for antibiotics, and further increase the substantial cost of medical care for these infants (8, 17). Staphylococci, including coagulase-negative staphylococci (CONS) and Staphylococcus aureus, are responsible for between 56 and Ͼ75% of hospital-acquired, late-onset neonatal sepsis (13, 31). Recent reports (12,28,30) show continuing increases in resistance of staphylococci to antimicrobial agents. Frequent and prolonged exposures to antimicrobials have been demonstrated to increase the risk of developing infections with resistant organisms (30,34). Therapeutic products and strategies that could prevent infections would minimize the need for antimicrobial products (20).Lipoteichoic acid (LTA) is a highly conserved epitope in the staphylococcal cell wall that inhibits phagocytosis of bacteria in vitro, induces the cytokine cascade through stimulation of Tolllike receptors, and may be necessary for staphylococcal survival (18, 19, 24, 27). An anti-LTA murine/human chimeric monoclonal antibody, pagibaximab, was developed by recombinant DNA ...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Phase 1/2 Double-Blind, Placebo-Controlled, Dose Escalation, Safety, and Pharmacokinetic Study of Pagibaximab (BSYX-A110), an Antistaphylococcal Monoclonal Antibody for the Prevention of Staphylococcal Bloodstream Infections, in Very-Low-Birth-Weight Neonates

Weisman

Thackray²,

Garcia‐Prats

et al. 2009

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…Pharmacokinetic analysis suggested a biphasic elimination curve and a terminal elimination half-life of 24.2 days. No toxicity was observed (28).…”

Section: Immunoglobulins In Neonatesmentioning

confidence: 91%

“…The pharmacokinetics and safety of IVIG were examined in thirty neonates with suspected sepsis who were randomly assigned either to a treatment (receiving either 250, or 500, or 1,000 mg/kg of IVIG plus antibiotics) or control (antibiotics alone) group (28). The 500 mg/kg dose produced a rise in total IgG for greater than 8 and in group B streptococcus typespecific IgG for greater than 4-14 days.…”

Section: Immunoglobulins In Neonatesmentioning

confidence: 99%