Safety of an Intravenous Formulation of Voriconazole as an Intramuscular Injection in Pigeons (Columba livia f. domestica).

Abstract

Aspergillosis is a common disease in birds. Currently, avian aspergillosis is treated with voriconazole administered orally, although intramuscular (IM) administration increases bioavailability and is more effective in treating generalized aspergillosis. The objective of this study was to evaluate the safety of the intravenous formulation of voriconazole as an IM injection in the pectoral muscles of pigeons (Columba livia f. domestica) as a model for other avian species. Sixteen healthy pigeons received IM injections of voriconazole (12.5 mg/kg) and sterile saline in the right and left pectoral muscles, respectively, twice a day for 7 days. Additionally, 4 birds acted as controls (no injections). Eight birds in the treatment group and 2 of the control pigeons were humanely euthanized 1 day (group 1) and 14 days (group 2) after the final injection. Hematologic and plasma biochemistry panels were performed prior to the birds being euthanized. Gross and histopathological evaluations of the pectoral muscles were completed postmortem. Statistical analysis revealed significant differences in multiple parameters, including aspartate aminotransferase and lactate dehydrogenase, but all biochemical analytes remained within the reference intervals for the species. The group 1 birds had advanced gross and histopathological pectoral muscle lesions associated with the voriconazole injections compared with the contralateral side, the group 2 birds, and the negative controls. After 14 days, the pectoral muscles did not reveal any gross or histopathological changes associated with the voriconazole or sterile saline injections. These results indicate that the intravenous formulation is safe for IM use twice per day for 1 week in pigeons. Further investigation is needed to extrapolate these findings to other avian species and to evaluate the roles of longer treatment periods and higher doses of voriconazole.