Premium
Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans
Author(s) -
Nagy Christa F.,
Leach Timothy S.,
King Alex,
Guttendorf Robert
Publication year - 2018
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.410
Subject(s) - bacillus anthracis , medicine , anthrax vaccines , immunogenicity , pharmacokinetics , tolerability , pharmacology , intramuscular injection , bioavailability , pharmacodynamics , antibody , anesthesia , adverse effect , immunology , immunization , dna vaccination , genetics , bacteria , biology
Abstract Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis . Obiltoxaximab, a high‐affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate. Here, we explored the safety, pharmacokinetics (PK), and immunogenicity of obiltoxaximab administered by intramuscular injection at doses of 4, 8, 16, 20, and 24 mg/kg in healthy humans. Systemic exposures were approximately dose proportional, maximum serum concentrations were observed after 6–9 days, and terminal half‐life ranged from 16 to 23 days. Average absolute intramuscular bioavailability was 64%. Obiltoxaximab was well tolerated, and local tolerability was acceptable up to 24 mg/kg intramuscularly, up to 6 injections per dose, and up to 5 mL per injection. No injection‐site abscesses or hypersensitivity reactions occurred; no subjects developed treatment‐emergent antitherapeutic antibodies over the study period of 71 days.