Initial evaluation of human monoclonal anti-lipid A antibody (HA-1A) in patients with sepsis syndrome

C. J. Fisher, J. Zimmerman, M. B. Khazaeli, Timothy E Albertson, R. P. Dellinger, Edward A Panacek, G. E. Foulke, C. Dating, C. R. Smith, A. F. LoBuglio

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34 Scopus citations

Abstract

HA-1A, a human monoclonal immunoglobulin M antibody that binds specifically to the lipid A domain f endotoxin, was administered to septic patients to evaluate the safety, pharmacokinetics, and immunogenicity of the antibody. Thirty-four patients received a single infusion of either 25 mg, 100 mg, or 250 mg, and were followed clinically for 14 to 21 days after treatment. HA-1A serum levels were measured before infusion and frequently after infusion with a radiometric assay. A one-compartment pharmacokinetic model was fit to the measured serum levels, and accurately described the changes in HA-1A level over time in each dose group (r2 = .99). The mean ± SEM apparent volume of distribution of HA-1A was 48.5 ± 4.5 ml/kg, and the mean serum clearance was 2.8 ± 0.4 ml/kg·h. The mean serum half-life of HA-1A was 15.9 ± 1.5 h. The mean serum level one hour after a 100-mg dose was 33.2 ± 2.4 μg/ml, and the mean concentration 24 h later was 9.1 ± 1.6 μg/ml. The dose administered and presence of Gram-negative bacterial infection did not significantly influence the volume of distribution or serum clearance. No adverse reactions to HA-1A were observed, and no antibodies against HA-1A were detected in any patient. These data indicate that the pharmacokinetics of HA-1A are well described by a one-compartment pharmacokinetic model, and that HA-1A is safe and nonimmunogenic in patients with sepsis.

Original languageEnglish (US)
Pages (from-to)1311-1315
Number of pages5
JournalCritical Care Medicine
Volume18
Issue number12
StatePublished - 1990
Externally publishedYes

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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    Fisher, C. J., Zimmerman, J., Khazaeli, M. B., Albertson, T. E., Dellinger, R. P., Panacek, E. A., Foulke, G. E., Dating, C., Smith, C. R., & LoBuglio, A. F. (1990). Initial evaluation of human monoclonal anti-lipid A antibody (HA-1A) in patients with sepsis syndrome. Critical Care Medicine, 18(12), 1311-1315.