Abstract
Actue, subacute and chronic toxicities of sulbactam (SBT), a new β-lactamase inhibitor, and SBT/CPZ were evaluated in Sprague-Dawley rats or ICR mice.
The acute intravenous LD50 of SBT or SBT/CPZ were estimated to be greater than 6000mg/kg in rats and mice.
In the subacute intravenous toxicity tests, all rats treated with SBT (30, 100, 300, 600, 1200mg/kg) or SBT/CPZ (300/300, 600/600mg/kg) for 1 month were well tolerated, and non-toxic dose of SBT is considered to be 100mg/kg. The higher dose levels (300, 600, 1200mg/kg) of SBT produced slight increases of the liver and cecum weights and a deposition of glycogen-like droplets in the hepatic cell cytoplasm withotit any functional abnormality and morphological lesions. SBT/CPZ groups, however, showed less degree of deposition than those of SBT groups, and the combination groups had no evidence of increase in liver weight.
In the chronic toxicity test, the rats treated intraperitoneally with SBT (25, 50, 250, 500mg/kg), CPZ (250, 500mg/kg) or SBT/CPZ (250/500, 500/250, 500/500mg/kg) for 6 months were well tolerated and the results were comparable to those in the subacute toxicity tests. The non-toxic dose in the chronic intraperitoneal toxicity test with SBT is considered to be 50mg/kg, and SBT did not enhance the toxicity when combined with CPZ.
