Studies on the Metabolism of Troglitazone to Reactive Intermediates in Vitro and in Vivo. Evidence for Novel Biotransformation Pathways Involving Quinone Methide Formation and Thiazolidinedione Ring Scission

Henry R. R., 1997, Thiazolidinones. Curr. Ther. Diabetes 26, 553−573

Gitlin N., 1998, Ann. Intern. Med., 129, 41, 10.7326/0003-4819-129-1-199807010-00008

Neuschwander-Tetri B. A., 1998, Ann. Intern. Med., 129, 38, 10.7326/0003-4819-129-1-199807010-00009

Watkins P. B., 1998, N. Engl. J. Med., 338, 10.1056/NEJM199803263381314

European Patent EP 0 441 605 A2 (1991).

Yoshioka T., 1989, J. Med. Chem., 32, 10.1021/jm00122a022

Hu J., 1999, J. Org. Chem., 64

Hart T. W., 1985, Tetrahedron Lett., 26

Baillie T. A., 1993, Mass spectrometry in the analysis of glutathione conjugates. Biol. Mass Spectrom. 22, 319−325

Davis, M. R., Kassahun, K., Jochheim, C. M., Brandt, K. M., and Baillie, T. A. (1993) Glutathione andN-acetylcysteine conjugates of 2-chloroethyl isocyanate. Identification as metabolites ofN,N‘-Bis(2-chloroethyl)-N-nitrosourea in the rat and inhibitory properties toward glutathione reductase in vitro.Chem. Res. Toxicol.6, 376−383.

Kassahun K., 1997, Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat:  Identification of Phase I metabolites and glutathione conjugates. Chem. Res. Toxicol. 10, 1228−1233

Borel A. G., 1993, Identification of carbomoylated thiol conjugates as metabolites of the antineoplastic 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, in rats and humans. Drug Metab. Dispos. 21, 889−901

Kassahun, K., Hu, P., Grillo, M. P., Davis, M. R., Jin, L., and Baillie, T. A. (1994) Metabolic activation of unsaturated derivatives of valproic acid. Identification of novel glutathione adducts formed through coenzyme A-dependent and -independent processes.Chem.Biol. Interact.90, 253−275.

Kawai K., 1997, Disposition and metabolism of the new oral antidiabetic drug troglitazone in rats, mice and dogs. Arzneim.-Forsch. 47, 356−368

Loi C. M., 1997, J. Clin. Pharmacol., 37

Ohe, T., Mashino, T., and Hirobe, M. (1994) Novel metabolic pathways of arylethers by cytochrome P450:  Cleavage of the oxygen-aromatic ring bond accompanyingipso-substitution by the oxygen atom of the active species in cytochrome P450 models and cytochrome P450.Arch. Biochem. Biophys.310, 402−409.

Ohe T., 1997, Substituent elimination from p-substituted phenols by cytochrome P450. ipso-Substitution by the oxygen atom of the active species. Drug Metab. Dispos. 25, 116−122

Ohe T., 2000, Novel metabolic pathway of estrone and 17β-estradiol catalyzed by cytochrome P-450. Drug Metab. Dispos. 28, 110−112

Yamazaki H., 1999, Oxidation of troglitazone to a quinone-type metabolite catalyzed by cytochrome P-450 2C8 and P-450 3A4 in human liver microsomes. Drug Metab. Dispos. 27, 1260−1266

He K., 1999, Proceedings of the 9th North American ISSX Meeting, #207

Polsker G. L., 1999, Troglitazone. A review of its use in the management of type 2 diabetes mellitus. Drugs 57, 409−438

Kohlroser J., 2000, Am. J. Gastroenterol., 95, 10.1111/j.1572-0241.2000.01707.x

Ramachandran V., 1999, Troglitazone increases cytochrome P-450 3A protein and activity in primary cultures of human hepatocytes. Drug Metab. Dispos. 27, 1194−1199

Mansuy D., 1991, J. Am. Chem. Soc., 113

Abbreviations TZD, thiazolidinedione