Abstract
Aim Enflicoxib, a selective COX-2 inhibitor approved for the treatment of
pain and inflammation associated with osteoarthritis in dogs
(Daxocox® [Ecuphar/Animalcare Group]) was
assessed for its genotoxic potential in a battery of in vitro and in
vivo genotoxicity assays. These comprised a bacterial reverse mutation
assay (Ames test), an in vitro human lymphocyte chromosome aberration
assay and an in vivo mouse bone marrow micronucleus assay.
Methods Relevant vehicle and positive control cultures and animals were
included in all assays. In the Ames test, enflicoxib was tested at
concentrations of up to 5000 μg/plate. Signs of
cytotoxicity were observed at the highest tested concentrations for several of
the bacterial strains, both in absence and presence of S9. In human lymphocytes,
enflicoxib was assessed for the induction of chromosomal aberrations when
exposed at concentrations of up to 62.5 (3 hours) and
29.6 µg/mL (20 hours) in the absence of S9, and
up to 66.7 µg/mL (3 hours) in presence of S9.
Signs of cell toxicity, evidenced as a decrease in the mitotic index, were
observed at these concentrations. In the mouse micronucleus assay, enflicoxib
dose levels of up to 2000 mg/kg were administered (single dose)
to male and female animals, and bone marrow samples were taken 24 and
48 hours (high-dose animals only) after administration.
Results Enflicoxib was shown to lack genotoxic activity in the conducted
assays.
Conclusions The administration of enflicoxib as a therapeutic analgesic
agent would not pose a genotoxic risk to animals or humans.
Key words
Enflicoxib - Daxocox - Genotoxicity - Mutagenesis - COX-2
