PMID: 11915367Mar 28, 2002Paper

Chronic toxicity in monkeys with the thiazolidinedione antidiabetic agent troglitazone

The Journal of Toxicological Sciences
Charles RothwellFelix A de la Iglesia

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 micrograms.hr/ml of troglitazone, 401 to 2060 micrograms.hr/ml of its sulfate conjugate, and 34 to 312 micrograms.hr/ml of its quinone metabolite. The...Continue Reading

References

Sep 30, 1993·The New England Journal of Medicine·UNKNOWN Diabetes Control and Complications Trial Research GroupC Siebert
Mar 28, 1998·The New England Journal of Medicine·P B Watkins, R W Whitcomb

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Citations

Feb 6, 2004·Clinical and Experimental Pharmacology & Physiology·Kenji ArakawaAkira Saito
Oct 7, 2009·Pharmacological Reviews·Xiaomin DengRobert A Roth
Nov 28, 2006·Life Sciences·Kris L Snow, Richard H Moseley
Aug 9, 2006·Toxicology Letters·Rawiwan ManiratanachoteTsuyoshi Yokoi
Aug 21, 2007·Journal of Computational Chemistry·Maykel Cruz-MonteagudoFernanda Borges
Jan 20, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mario Chojkier
Aug 7, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Crystal R WaitesBeth E Schilling
Jun 17, 2003·Chemical Research in Toxicology·Martyn T Smith

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