Metabolic activation of pioglitazone identified from rat and human liver microsomes and freshly isolated hepatocytes

Drug Metabolism and Disposition

Volumn 33, Issue 6, 2005, Pages 733-738

  Baughman, T M ^a   Graham, R A ^a   Wells Knecht, K ^a,c   Silver, I S ^a   Tyler, L O ^a   Wells Knecht, M ^a   Zhao, Z ^b  

^a GLAXOSMITHKLINE   (United States)

^b AMGEN INC   (United States)

^c MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG METABOLITE; GLUTATHIONE; PIOGLITAZONE;

ANIMAL CELL; ARTICLE; CELL ISOLATION; DRUG CONJUGATION; DRUG METABOLISM; DRUG STRUCTURE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; LIVER CELL; LIVER MICROSOME; METABOLIC ACTIVATION; NONHUMAN; PRIORITY JOURNAL; RAT; RING OPENING; TANDEM MASS SPECTROMETRY;

ANIMALS; HEPATOCYTES; HUMANS; MALE; MICROSOMES, LIVER; RATS; RATS, SPRAGUE-DAWLEY; SPECIES SPECIFICITY; THIAZOLIDINEDIONES;

EID: 18844456597     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.104.002683     Document Type: Article

References (23)

1. Alvarez-Sanchez R and Paehler A (2004) Glutathione conjugates after thiazolidinedione ring opening: a comparison of the bioactivation of troglitazone, rosiglitazone and pioglitazone in vitro. Drug Metab Rev 36:172.
2. Chase MP and Yarze JC (2002) Pioglitazone-associated fulminant hepatic failure. Am J Gastroenterol 97:502-503.
3. Chen WG, Zhang C, Avery MJ, and Fouda HG (2001) Reactive metabolite screen for reducing candidate attrition in drug discovery. Adv Exp Med Biol 500:521-524.
4. Cleland WW (1964) Dithiothreitol, a new protective reagent for SH groups. Biochemistry 3:480-482.
5. Eckland DA and Danhof M (2000) Clinical pharmacokinetics of pioglitazone. Exp Clin Endocrinol Diabetes 108 (Suppl 2):S234-S242.
6. Faich GA and Moseley RH (2001) Troglitazone (Rezulin) and hepatic injury. Pharmacoepidemiol Drug Saf 10:537-547.
7. Gitlin N, Julie NL, Spurr CL, Lim KN, and Juarbe HM (1998) Two cases of severe clinical and histologic hepatotoxicity associated with troglitazone. Ann Intern Med 129:36-38.
8. Kassahun K, Pearson PG, Tang W, McIntosh I, Leung K, Elmore C, Dean D, Wang R, Doss G, and Baillie TA (2001) 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. Chem Res Toxicol 14:62-70.
9. Kiyota Y, Kondo T, Maeshiba Y, Hashimoto A, Yamashita K, Yoshimura Y, Motohashi M, and Tanayama S (1997) Studies on the metabolism of the new antidiabetic agent pioglitazone. Identification of metabolites in rats and dogs. Arzneim-Forsch 47:22-28.
10. Krieter PA, Colletti AE, Doss GA, and Miller RR (1994) Disposition and metabolism of the hypoglycemic agent pioglitazone in rats. Drug Metab Dispos 22:625-630.
11. Maeda K (2001) Hepatocellular injury in a patient receiving pioglitazone. Ann Intern Med 135:306.
12. May LD, Lefkowitch JH, Kram MT, and Rubin DE (2002) Mixed hepatocellular-cholestatic liver injury after pioglitazone therapy. Ann Intern Med 136:449-452.
13. Nelson SD (2001) Structure toxicity relationships - how useful are they in predicting toxicities of new drugs? Adv Exp Med Biol 500:33-43.
14. Neuschwander-Tetri BA, Isley WL, Oki JC, Ramrakhiani S, Quiason SG, Phillips NJ, and Brunt EM (1998) Troglitazone-induced hepatic failure leading to liver transplantation. A case report. Ann Intern Med 129:38-41.
15. Prabhu S, Fackett A, Lloyd S, McClellan HA, Terrell CM, Silber PM, and Li AP (2002) Identification of glutathione conjugates of troglitazone in human hepatocytes. Chem-Biol Interact 142:83-97.
16. Sahi J, Black CB, Hamilton GA, Zheng X, Jolley S, Rose KA, Gilbert D, LeCluyse EL, and Sinz MW (2003) Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos 31:439-446.
17. Seglen PO (1976) Preparation of isolated rat liver cells. Methods Cell Biol 13:29-83.
18. Shen Z, Reed JR, Creighton M, Liu DQ. Tang YS, Hora DF, Feeney W, Szewczyk J, Bakhtiar R, Franklin RB, et al. (2003) Identification of novel metabolites of pioglitazone in rat and dog. Xenobiotica 33:499-509.
19. Smith MT (2003) Mechanisms of troglitazone hepatotoxicity. Chem Res Toxicol 16:679-687.
20. Sohda T, Ikeda H, and Meguro K (1995) Studies on antidiabetic agents. XII. Synthesis and activity of the metabolites of (+/-)-5(-)[p(-)[2-(5-ethyl-2- pyridyl)ethoxy)benzyl]-2,4- thiazolidinedione (pioglitazone). Chem Pharm Bull (Tokyo) 43:2168-2172.
21. Tanis SP, Parker TT, Colca JR, Fisher RM, and Kletzein RF (1996) Synthesis and biological activity of metabolites of the antidiabetic, antihyperglycemic agent pioglitazone. J Med Chem 39:5053-5063.
22. Tolman KG and Chandramouli J (2003). Hepatotoxicity of the thiazolidinediones. Clin Liver Dis 7(2):369-379, vi.
23. Watkins PB and Whitcomb RW (1998) Hepatic dysfunction associated with troglitazone. N Engl J Med 338:916-917.