The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Regular Paper
CHRONIC TOXICITY IN MONKEYS WITH THE THIAZOLIDINEDIONE ANTIDIABETIC AGENT TROGLITAZONE
Charles ROTHWELLEdward J. MCGUIREDouglas M. ALTROGGEHiroshi MASUDAFelix A. de la IGLESIA
Author information
JOURNALS FREE ACCESS

2002 Volume 27 Issue 1 Pages 35-47

Details
Abstract

The antidiabetic agent troglitazone was given to groups of 4 cynomolgus monkeys per sex at 300, 600, or 1200 mg/kg daily by gavage for 52 weeks. A group of 4 monkeys per sex received vehicle alone and served as controls. Emesis and soft stool or diarrhea occurred sporadically in all troglitazone-treated groups, but did not compromise animal health. There were no effects on body weight or food consumption, or ophthalmologic, electrocardiographic, or echocardiographic parameters. Erythrocyte count, hemoglobin, and hematocrit decreased 8% to 16% in males at all doses and serum cholesterol decreased 30% to 46% in both sexes at all doses. Urinary ketones were increased in several animals at 600 and 1200 mg/kg. Absolute and relative liver weights increased at all doses in both sexes by 40% to 71%. The only microscopic change attributable to troglitazone treatment was minimal to mild bile duct hyperplasia in males at all doses and in females at 600 and 1200 mg/kg. No differences in systemic exposure were apparent between sexes. Over the dose range tested, AUC(0-24) values were 27 to 102 μg·hr/ml of troglitazone, 401 to 2060 μg·hr/ml of its sulfate conjugate, and 34 to 312 μg·hr/ml of its quinone metabolite. Therefore, oral administration of troglitazone to monkeys at 300, 600, and 1200 mg/kg for 52 weeks resulted in significant systemic exposure, with only minimal gastrointestinal, hematologic, and hepatic effects.

Information related to the author
© 2002 The Japanese Society of Toxicology
Previous article Next article
feedback
Top