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Pioglitazone HCl was not mutagenic in a battery of genetic toxicology studies, includ-ing the Ames bacterial assay, a mammalian cell forward gene mutation assay (CHO/ HPRT and AS52/ XPRT), an in vitro cytogenetics assay using CHL cells, an unscheduled DNA syn-thesis assay, and an in vivo micronucleus assay. No adverse effects upon fertility were observed in male and female rats at oral doses up to 40 mg/ kg pioglitazone HCl daily prior to and throughout mating and gestation (approximately 9 times the maximum recommended human oral dose based on mg/ m 2 ). Animal Toxicology Heart enlargement has been observed in mice (100 mg/ kg), rats (4 mg/ kg and above) and dogs (3 mg/ kg) treated orally with pioglitazone HCl (approximately 11, 1, and 2 times the maximum recommended human oral dose for mice, rats, and dogs, respectively, based on mg/ m 2 ). In a one-year rat study, drug-related early death due to apparent heart dysfunc-tion occurred at an oral dose of 160 mg/ kg/ day (approximately 35 times the maximum rec-ommended human oral dose based on mg/ m 2 ). Heart enlargement was seen in a 13-week study in monkeys at oral doses of 8.9 mg/ kg and above (approximately 4 times the max-imum recommended human oral dose based on mg/ m 2 ), but not in a 52-week study at oral doses up to 32 mg/ kg (approximately 13 times the maximum recommended human oral dose based on mg/ m 2 ). Text Continues Below
Pregnancy Pregnancy Category C. Pioglitazone was not teratogenic in rats at oral doses up to 80 mg/ kg or in rabbits given up to 160 mg/ kg during organogenesis (approximately 17 and 40 times the maximum recommended human oral dose based on mg/ m 2 , respectively). Delayed parturition and embryotoxicity (as evidenced by increased postimplantation losses, delayed development and reduced fetal weights) were observed in rats at oral doses of 40 mg/ kg/ day and above (approximately 10 times the maximum recommended human oral dose based on mg/ m 2 ). Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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