[Studies of the effects of sibutramine hydrochloride on perinatal development and maternal function in mice].

OBJECTIVE

To detect adverse effects on the pregnant/lactating dams and on the development of the offspring following exposure to sibutramine hydrochloride of the dams from the closure of the hard palate through weaning.

METHODS

Studies on the effects of this new drug on pre- and postnatal development, including maternal function of mice were conducted. The pregnant mice were randomly divided into four groups. The dose levels were 32 mg/(kg.d) (1/5 LD50), 2.83 mg/(kg.d), 0.25 mg/(kg.d) for three groups respectively, and the fourth group was for negative control. Females were administered sibutramine hydrochloride in drink water from the closure of the hard palate (pregnant 15 d) to the end of lactation. Adverse effects on pregnant mice, pre- and postnatal deaths of offspring, altered growth and development, functional deficits in offspring were assessed. Terminal examinations included: necropsy (macroscopic examination) of all adults, abnormalities, live offspring at birth, body weight at birth, pre- and postweaning survival and growth/body weight, maturation, physical development, sensory functions and reflexes and behavior.

RESULTS

The increase of death (above 10%) of pregnant and lactating mice was observed in the group of 32 mg/(kg.d). No other adverse effects on the maternal animals and offspring were observed.

CONCLUSION

The data of these studies on mice showed no evidence for the reproductive toxicity to pregnant mice and the developmental toxicity to offspring induced by sibutramine hydrochloride.