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trimebutine maleates chronic toxicity

Time:2015/9/30 7:12:20

Trimebutine maleate was administered orally for 26 weeks to rats and beagle dogs at dose levels of 40, 220 and 1,210 mg/kg/day or 10, 30 and 90 to 250 mg/kg/day, respectively.

In rats, no overt clinical signs nor identifiable specific target organ toxicity were observed. In the high dose groups, a low incidence of mortality occurred. Weight gain

decreased at 1,210 mg/kg/day in males and females and in females dosed with 220 mg/kg/day. A moderate elevation of SAP and SGPT appeared at the end of the treatment

period in the high dose female group. At 1,210 mg/kg/day, liver and adrenal weights (relative to body weights) were increased, while kidney weights increased in the high

dose groups. Histopathological examination did not reveal any abnormalities.

In dogs, adverse clinical signs and weight loss were confined to animals dosed at 250mg/kg/day. A dose related decreased coagulation time was observed at 90 and 250

mg/kg/day, which was also associated with reduced prothrombin time. At the high dose level, serum albumin decreased while blood urea nitrogen, blood creatinine and liver,

kidney or adrenal weights increased. There were no histopathological abnormalities considered related to treatment. 


trimebutine maleate teratology


In rats, teratogenicity studies, fertility and general reproductive studies and pre and postnatal studies were undertaken by the oral and i.m. routes at doses of 100-1,000 mg/kg

and 12.5-50 mg/kg, respectively. In teratogenicity studies in rabbits, trimebutine maleate was administered orally and subcutaneously at doses of 50-200 mg/kg and 25-100 mg/kg,

respectively. 


trimebutine maleate mutagenicity


No teratogenic abnormalities were found during the course of these studies and trimebutine maleate had no adverse effects on fertility, reproduction, course and outcome

of pregnancy and offspring development during lactation.

In vivo, mutagenicity study in mice at dose levels of 3,000-12,000 mg/kg and in vitro mutagenicity and carcinogenicity studies failed to show any evidence of bone marrow

toxicity or mutagenic and carcinogenic potential of trimebutine maleate.