fce-22891 and Kidney-Diseases

LD50 values of FCE 22101 iv were 3872 mg/kg and 4392 mg/kg in male and female mice, and 2000 mg/kg and 2201 mg/kg in male and female rats respectively. Oral LD50s of FCE 22891 were 4363 mg/kg in male and 6167 mg/kg in female mice; in the rat this value was over 5000 mg/kg in both males and females. FCE 22101, given iv for two consecutive days was less nephrotoxic in rabbits than cephaloridine and imipenem alone, but more nephrotoxic than imipenem/cilastatin. Dose ranging studies carried out in rats and 13-week studies in rats and monkeys indicated that the kidney was a target organ for both penem compounds. Renal lesions appeared beginning with doses higher than 300 mg/kg/day and were morphologically similar to those induced by cephaloridine and imipenem. Possible targets at high doses were the urinary bladder in rats and the haemopoietic system in monkeys given FCE 22101. The toxicity data available for iv FCE 22101 and oral FCE 22891 in the rat and monkey indicated an adequate tolerance of these compounds, comparable with other beta-lactam antibiotics, including imipenem/cilastatin.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Female; Kidney Diseases; Lactams; Lethal Dose 50; Male; Mice; Mice, Inbred Strains; Rats; Time Factors