mirosamicin and Body-Weight

A 28-day oral dosage test of miporamicin (MPM), a new macrolide antibiotic, was performed to assess its toxicologic potential in groups of male and female rats receiving the compound in feed. Five graded dosage levels of 0, 3,200, 8,000, 20,000, and 50,000 ppm were employed for treatment with MPM in feed and the treatment period was followed by a 28-day recovery phase observation period. 1. No deaths occurred throughout the course of the experiment. Animals receiving 50,000 ppm developed signs: ruffled hair coat and emaciation, which disappeared following withdrawal of the drug. 2. The MPM-50,000 group displayed depression of weight gain and decrease of feed and water intake during the treatment period. During the posttreatment recovery phase observation period the animals showed recovery in weight gain rate as well as in feed and water intake. 3. The achieved compound dosage was 273 mg/kg/day in males and 288 mg/kg/day in females in the MPM-3,200 group, 721 and 773 mg/kg/day respectively in the MPM-8,000 group, 1,738 and 1,856 mg/kg/day in the MPM-20,000 group, and 3,405 and 3,611 mg/kg/day in the MPM-50,000 group. 4. Hematological examinations revealed low values for RBC, WBC, hematocrit and hemoglobin concentration and decreased platelet counts in the MPM-50,000 group, which were considered to be due to the decreased feed intake. These changes disappeared or abated following withdrawal. 5. Of various serum biochemical parameters assessed, total protein, albumin, glucose and triglycerides showed lowered values in the MPM-50,000 group. All these changes were considered to be attributable to the decreased feed intake. During the ensuing recovery phase observation period, all these parameters showed restoration or abatement in parallel with the recovery in feed intake. 6. Urine analysis disclosed decrease of urine volume, lowered electrolyte concentration and elevation of urine osmolarity in the MPM-20,000 and the MPM-50,000 groups. These changes were considered to be secondary to cecal enlargement which is commonly seen with antibiotic medication, or to the decreased feed and water intake. Following drug withdrawal, all these changes disappeared with the recovery in feed and water intake and abatement of cecal hyperplasia. 7. At terminal necropsy, diminution of body fat and atrophy of the spleen and thymus that correlated with emaciation were noted in the MPM-50,000 group. Dose-related enlargement of the caecum was also noted in the treated groups. All th

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Blood; Blood Cell Count; Body Weight; Chemical Phenomena; Chemistry; Diet; Drinking; Eating; Female; Macrolides; Male; Organ Size; Rats; Rats, Inbred Strains; Time Factors; Urine

A six-month oral toxicity test of the new macrolide antibiotic miporamicin (MPM) was carried out in male and female rats receiving the compound in feed at concentrations of 1,280, 3,200, 8,000, or 20,000 ppm. The animals were further observed for recovery for 2 months after the completion of the treatment period. 1. No death occurred at any dosage levels throughout the study period. The only notable signs observed were marginal blepharitis and aging-associated changes that were seen occasionally among the treated and control rats. There were no symptomatic changes of particular note. 2. Body weight, feed intake and water consumption data did not reveal any noticeable change. 3. The achieved test compound intake was 69 mg/kg/day for males and 82 mg/kg/day for females in the MPM-1,280 group, 176 mg/kg/day for males and 207 mg/kg/day for females in the MPM-3,200 group, 436 mg/kg/day for males and 519 mg/kg/day for females in the MPM-8,000 group, and 1,080 mg/kg/day for males and 1,280 mg/kg/day for females in the MPM-20,000 group. 4. No changes attributable to these treatments were noted in the hematological examination or serum biochemical tests. 5. Urinalysis disclosed mild changes with respect to urine volume, urinary electrolyte concentration and osmolarity. Animals recovered from all these changes during the recovery phase observation. 6. At gross pathologic examination a dose-related enlargement of the caecum was observed. The change disappeared or diminished following the 2-month recovery phase observation. 7. Organ weight analysis showed a dose-related increase of weight of the caecum. Animals recovered or abated in this respect during the 2-month recovery phase observation. 8. Histopathologic examination revealed no adverse toxicologic changes other than spontaneous or aging-associated ones. 9. No abnormalities were noted in the liver or in the kidneys as examined by electron microscopy. 10. The maximum non-effective level of MPM thus was estimated to be 20,000 ppm at which no organic damage occurred.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Blood; Blood Cell Count; Body Weight; Chemical Phenomena; Chemistry; Diet; Drinking; Eating; Female; Macrolides; Male; Organ Size; Rats; Rats, Inbred Strains; Time Factors; Urine

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