Skin and mucous membrane ulceration in beagle dogs following oral dosing with an experimental aminoglycoside antibiotic

Abstract

G-418 is a unique aminoglycoside antibiotic that is structurally related to gentamicin; however, unlike gentamicin, G-418 inhibits growth of both procaryotic and eucaryotic cells. In a preliminary acute oral safety study, adult male and female beagles were given a single oral dose of either 2000, 1000, 500, 200, or 50 mg/kg of G-418. Ulceration of the lip, tongue, and/or gingiva occurred in all G-418-dosed dogs 1 to 9 days after dosing. Ulceration of the glans penis, penis sheath, and scrotum occurred 7 to 14 days after a single oral dose with 1000 and 500 mg/kg G-418, and ulceration of the vaginal mucosa of the 2000-, 1000-, 500-, and 50-mg/kg-dosed female dogs occurred 2 to 8 days after dosing. Ulcers of the lip and vaginal area began at the mucocutaneous border and were more severe at these borders. In some dogs a yellow membrane formed over these lesions. Ulceration of the oral and vaginal mucosa disappeared 10 days after the first occurrence and reoccurred 3–7 days later. All ulcers healed within 30 days after the single oral dose; however, at necropsy hemorhagic areas of the urinary bladder were observed in at least one of two dogs at each dose level. Similar lesions have not been reported in animals treated with any other aminoglycoside antibiotics. The etiology of these lesions is unknown.