ANTHIM Clinical Pharmacology Card
ANTHIM (obiltoxaximab) injection
Mechanism of Action
|Obiltoxaximab is a deimmunized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that specifically binds the protective antigen (PA) of B. anthracis, thereby preventing its association with the anthrax toxin receptor on host cells.
|Because the effectiveness of ANTHIM cannot be evaluated in humans, a comparison of ANTHIM exposures achieved in healthy human subjects to those observed in animal models of inhalational anthrax in therapeutic efficacy studies. Based on observed and simulated data, healthy subjects and humans infected with B. anthracis achieve similar obiltoxaximab median Cmax and 2-fold greater median AUCinf following a single 16 mg/kg IV dose compared to exposures associated with efficacy in rabbits and monkeys in inhalational anthrax efficacy studies.
|The PK of obiltoxaximab are linear over the dose range of 4 mg/kg (0.25 times the lowest recommended dose) to 16 mg/kg following single IV administration in healthy subjects.
Mean Cmax and AUCinf were 400 mcg/mL and 5170 mcg•day/mL, respectively, following a single 16 mg/kg IV dosing to healthy male and female subjects.
Mean obiltoxaximab steady-state volume of distribution was greater than plasma volume, suggesting some tissue distribution.
Terminal half-life is approximately 15 to 23 days in healthy 75 subjects.
Obiltoxaximab clearance was much smaller than the glomerular filtration rate indicating that there is virtually no renal clearance.
|Population pharmacokinetic analysis indicated that gender (female versus male), race (non-Caucasian versus Caucasian), or age (elderly versus young) had no meaningful effects on the PK parameters for ANTHIM.
|ANTHIM PK have not been evaluated in children
|Co-administration of 16 mg/kg ANTHIM intravenously with intravenous or oral ciprofloxacin in human subjects did not alter the PK of either ciprofloxacin or obiltoxaximab