The intravenous toxicity of dibekacin sulphate (DKB) to female beagle dogs.

Abstract

Dibekacin sulphate (DKB), a new aminoglycoside antibiotic developed on the theory of bacterial resistance, was given by intravenous injection to groups of female Beagle dogs at dosages of 2.5, 5.0, 10.0 or 25.0 mg/kg/day for 13 weeks. Physiological saline was given as a control. Some dogs given 5.0 or 10.0 mg/kg/day were retained undosed for a further 5 weeks in order to assess recovery. Premature deaths from acute renal tubular nephrosis occurred in dogs given 25.0 and 10.0 mg/kg/day. Dogs which survived treatment at 10.0 mg/kg/day showed marked elevation of circulating urea and creatinine concentrations after 4 weeks' treatment but thereafter the increases became less obvious. Varying degrees of renal cortical tubular dilatation, basophilia, degeneration or necrosis were seen in the kidneys of all dogs examined after 13 weeks treatment although no clinical impairment of renal function was detectable at dosages up to 5.0 mg/kg/day. These changes had essentially regressed in dogs examined 5 weeks after the last dose of DKB at 5.0 mg/kg/day. All the adverse clinical and histological effects noted, following any dose level of DKB tested, could be attributed to renal changes.