hr-810 and Fetal-Death

A teratogenicity study was performed in rats by intraperitoneal or intravenous administration of cefpirome sulfate (CPR) at dose level of 0 (control), 200, 400 and 800 mg/kg/day to dams from day 7 to day 17 of pregnancy. Twenty one to twenty eight female rats in each intraperitoneal and intravenous administrated group were sacrificed on day 21 of pregnancy for examination of their fetuses, and ten to thirteen female rats in each intraperitoneal administrated group were allowed to deliver for the postnatal examination of their offsprings. In the 800 mg/kg/day intravenous administrated group, two dams out of twenty four died during administration period, however no animal died in any intraperitoneal administrated group. The doses of 400 and 800 mg/kg/day caused piloerection, diarrhea or loose feces in the both administration routes, and accelerated breathing, a decrease in spontaneous activity, systemic spasms, cataleptic symptoms and wild running in the intravenous route. The suppression of body weight gain was detected in the 800 mg/kg/day intraperitoneal administrated group and 200, 400 and 800 mg/kg/day intravenous administrated groups, however there were no significant differences in food and water intakes between treated and control groups. At autopsy, enlargement of caecum and an increase in adrenal weight were detected in the 800 mg/kg/day groups of both administration routes. Body weight of the fetuses was decreased in both sexes in the 800 mg/kg/day group and in male fetuses in the 400 mg/kg/day group, and placental weight was decreased in the 800 mg/kg/day group, in the both administration routes respectively. However, embryonal or fetal mortality and incidences of external or visceral anomalies were not increased. In offspring, the dose of 800 mg/kg/day caused very slight suppression of body weight gain, however CPR had no adverse effects on the postnatal development such as viability, differentiation, emotionality, learning ability or reproductive performance. The results suggest that the non-effective dose level of CPR is 200 mg/kg/day in maternal animals and fetuses, 400 mg/kg/day in offsprings in intraperitoneal route, lower than 200 mg/kg/day in maternal animals and 200 mg/kg/day in fetuses in intravenous route respectively.

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Bone and Bones; Cefpirome; Cephalosporins; Dose-Response Relationship, Drug; Female; Fetal Death; Fetus; Male; Motor Activity; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Reproduction

A perinatal and postnatal study was performed in rats by intraperitoneal administration of cefpirome sulfate (CPR) at dose levels of 0 (control), 200, 400 and 800 mg/kg/day to dams from day 17 of pregnancy to day 21 after delivery. Twenty one or twenty two dams in each group were allowed to deliver for the postnatal examination of their offsprings. No animal died. Loose feces were observed in the 800 mg/kg/day group. Body weight gain of the dams was retarded in the 800 mg/kg/day group in the early stage of treatment. Food intake was reduced simultaneously in the 200, 400 and 800 mg/kg/day groups. Autopsy revealed the enlargement of caecum in the 800 mg/kg/day. The adrenal weight was increased in the 400 and 800 mg/kg/day groups, and the kidney weight was increased in the 800 mg/kg/day group. The body weight of pups at birth in the 800 mg/kg/day group was slightly lower than that in the control group. The body weight of male pups in the 800 mg/kg/day group decreased transiently during rearing period. However, CPR had no adverse effects on the postnatal development such as viability, differentiation, emotionality, learning ability or reproductive performance. The results suggest that the non-effective dose level of CPR is lower than 200 mg/kg/day for general toxicity, 800 mg/kg/day for reproductive ability in maternal animals and 400 mg/kg/day in offsprings respectively.

Topics: Abnormalities, Drug-Induced; Animals; Animals, Newborn; Body Weight; Cefpirome; Cephalosporins; Dose-Response Relationship, Drug; Female; Fetal Death; Fetus; Male; Motor Activity; Organ Size; Pregnancy; Rats; Rats, Inbred Strains; Reproduction