REPRODUCTION STUDIES WITH SULBACTAM AND COMBINATIONS OF SULBACTAM AND CEFOPERAZONE IN RATS

Abstract

Reproduction studies of sulbactam (SBT) and SBT/CPZ were conducted in Sprague-Dawley rats. Doses employed in these studies were 500, 250 and 50 mg/kg of SBT, and 500/500mg/kg of SBT/CPZ.
1) Fertility and general reproductive study
Male rats were treated intraperitoneally with SBT or SBT/CPZ for 62 days prior to mating and females were treated intravenously from 14 days prior to mating to day 7 of gestation. The reproductive performance parameters such as the rates of copulation and pregnancy in the SBT or SBT/CPZ groups were comparable to those of controls. No drug-related external, visceral or skeletal malformations were observed in the fetuses from the dams sacrificed on day 21 of gestation.
2) Teratological study
Pregnant rats were treated intravenously with SBT or SBT/CPZ from day 7 to day 17 of gestation. No drugrelated external, visceral or skeletal malformations of the fetuses were found. The parturition and nursing ability of the dams and the growth, viability, behavioral and reproductive performance of F₁ offsprings of SBT or SBT/CPZ groups were comparable to those of controls. No drug-related external malformations were noted in any of the F₂, fetuses.
3) Peri-and postnatal study
Pregnant rats were treated intravenously with SBT or SBT/CPZ from day 17 of gestation to day 21 of the postparturition. A slight decrease of survival rates of the pups at day 4 after birth in the groups treated with 500mg/kg of SBT or 500/500mg/kg of SBT/CPZ was found, but no significant decrease was noted thereafter. The postnatal development, fertility of offspring (F₁) and development of F₂ fetuses in the treated groups were comparable to those of controls.