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
Jan 1, 1992·Hypertension·J E HallH L Mizelle
Oct 1, 1991·Metabolism: Clinical and Experimental·L BowenG I Shulman
Nov 1, 1988·Diabetes·T FujiwaraH Horikoshi
May 1, 1995·Diabetes Research and Clinical Practice·Y OhkuboM Shichiri
Mar 1, 1995·American Journal of Hypertension·T OgiharaK Masuo
Dec 1, 1994·Diabetes·M K LeeJ M Olefsky
Sep 30, 1993·The New England Journal of Medicine·UNKNOWN Diabetes Control and Complications Trial Research GroupC Siebert
Jun 1, 1996·Diabetes·T KazumiG Yoshino
Feb 1, 1996·Diabetes Care·Y IwamotoT Kaneko
Dec 1, 1996·Diabetes·A R Saltiel, J M Olefsky
Mar 1, 1997·Diabetes·M N GhazziR W Whitcomb
Apr 1, 1996·Diabetic Medicine : a Journal of the British Diabetic Association·Y IwamotoT Kaneko
Feb 7, 1998·Annals of Internal Medicine·D G MaggsG I Shulman
Mar 20, 1998·Journal of Clinical Pharmacology·C M LoiA J Sedman
Mar 28, 1998·The New England Journal of Medicine·P B Watkins, R W Whitcomb
Sep 4, 1998·Diabetes Care·E S HortonR W Whitcomb
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
May 18, 2006·Leukemia Research·Chunhong GuRichard A Wells
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
Mar 20, 2021·Scientific Reports·Hubert DirvenKatya Tsaioun
Jun 17, 2003·Chemical Research in Toxicology·Martyn T Smith
Jan 14, 2009·Chemical Research in Toxicology·Shunji KuribayashiHiroshi Yamazaki