Parenteral toxicological profile of the monocyclic -lactam antibiotic SQ 26,776 in mice, rats and dogs

Abstract

The acute iv LD ₅₀ of SQ 26,776 (SQ) in mice was 3300 mg/kg, and the ip LD ₅₀ in rats was 6600 mg/kg. In dogs, SQ did not interfere with cardiovascular or renal function when given at iv doses as high as 1500 mg/kg. In 1 -month studies, SQ was administered sc to groups of 12 rats at total daily doses of 0, 150, 600 and 2400 mg/kg, and iv to groups of four dogs at total daily doses of 0, 40, 150 and 650 mg/kg. In both species, mild irritation was observed at the injection sites in animals given 600 mg/kg or more daily. Rats of both sexes given 600 and 2400 mg/kg sc had distention of the caecum and increased liver weights; no histopathological changes were found in these organs. Female rats given 2400 mg/kg daily sc showed evidence of a mild effect on the kidneys. The minor effects observed in animals given large doses of SQ were similar to, or less pronounced than, those caused by comparable parenteral doses of other β -lactam antibiotics. Thus, SQ demonstrated a low order of toxicity in mice, rats and dogs.