mirosamicin and Abnormalities--Drug-Induced

Experiments were conducted to assess the effects of miporamicin (MPM) on prenatal and postnatal development of fetuses and offsprings of rats receiving the compound at oral dosages of 40, 200, or 1,000 mg/kg/day during the organogenesis stage of gestation. The drug treatment had no appreciable effect on maternal body weight during pregnancy or lactation period. The rats showed decreased food intake and increased water intake during gestation period in the groups given greater than or equal to 200 mg/kg/day, and increased food and water intakes during lactation period in the group given 1,000 mg/kg/day. There was no macroscopic evidence of changes indicative of any effect of the treatment in the viscera of rat dams at terminal necropsy. Observation of the fetuses did not reveal any effect of the treatment with MPM with respect to the number of implantations, the number of living fetuses, the death rate of fetuses or incidence of external, visceral, or skeletal anomalies. Male fetal weights were low in the groups given greater than or equal to 200 mg/kg/day. Observation of the offspring post partum failed to disclose any abnormalities indicative of adverse effects of the treatment with respect to birth index, viability index, weaning index, postnatal external differentiation, body weight changes, external morphology, skeleton, viscera, organ weight, functional and behavioral tests, emotion, learning ability, or reproductive performance, or in respect of prenatal development of their fetuses (F2). It is concluded from the results that no effect dose levels of MPM was 40 mg/kg/day in rat dams, 40 mg/kg/day also for their fetuses, and 1,000 mg/kg/day for postnatal development of the offspring under the experimental conditions described.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Anti-Bacterial Agents; Behavior, Animal; Body Weight; Drinking; Eating; Embryonic and Fetal Development; Female; Fetal Death; Macrolides; Male; Organ Size; Pregnancy; Rats; Rats, Inbred Strains

A teratogenicity study on miporamicin (MPM) was performed in New Zealand White rabbits. Following suitable dose range finding experiments, 60 mated rabbits were randomised into 4 treatment groups, each containing 15 animals. These animals were dosed once daily, by oral gavage, over days 6-18 inclusive of gestation, where the day of mating was designated as day 0. The dose levels applied were 0, 50, 100 and 200 mg/kg/day. A standard dose volume of 5 ml dosing suspension per kilogram body weight was applied, the vehicle being an 0.5% solution of carboxymethylcellulose in distilled water. There was an effect on maternal food consumption at 200 mg/kg/day: cessation of consumption by over one quarter of the animals in the group. Under the conditions of this study, MPM had no effect on the outcome of pregnancy at dose levels of up to 200 mg/kg/day. There was generally no significant effect on either the mother or the conceptus at 100 mg/kg/day.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Anti-Bacterial Agents; Body Weight; Eating; Female; Macrolides; Pregnancy; Rabbits; Reproduction