ReviewDrug-Induced Idiosyncratic Hepatotoxicity: Prevention Strategy Developed after the Troglitazone Case
References (62)
- et al.
Involvement of the immune system in idiosyncratic drug reactions
Drug Metab. Pharmacokinet.
(2011) - et al.
Detection of autoantibody to aldolase B in sera from patients with troglitazone-induced liver dysfunction
Toxicology
(2005) - et al.
Formation of a novel quinone epoxide metabolite of troglitazone with cytotoxicity to HepG2 cells
Drug Metab. Dispos.
(2002) - et al.
Prediction of severe adverse drug reactions using pharmacogenetic biomarkers
Drug Metab. Pharmacokinet.
(2010) - et al.
Cytotoxicity and apoptosis produced by troglitazone in human hepatoma cells
Life Sci.
(2001) - et al.
Troglitazone, but not rosiglitazone, damages mitochondrial DNA and induces mitochondrial dysfunction and cell death in human hepatocytes
Toxicol. Appl. Pharmacol.
(2009) - et al.
Utility of microtiter plate assays for human cytochrome P450 inhibition studies in drug discovery: application of simple method for detecting quasi-irreversible and irreversible inhibitors
Drug Metab. Pharmacokinet.
(2004) - et al.
Quantitative assessment of reactive metabolite formation using 35S-labeled glutathione
Drug Metab. Pharmacokinet.
(2009) - et al.
A quantitative high-throughput trapping assay as a measurement of potential for bioactivation
Anal. Biochem.
(2006) - et al.
Liver dysfunction associated with troglitazone (Noscal)
J. Clin. Ther. Med.
(1998)
Was it not possible to predict liver dysfunction caused by troglitazone during the nonclinical safety studies?
Reevaluation of safety. Iyakuhin Kenkyu
Troglitazone. Handb. Exp. Pharmacol.
Various forms of chemically induced liver injury and their detection by diagnostic procedures
Environ. Health Perspect.
Role of innate immunity in acetaminophen-induced hepatotoxicity
Expert Opin. Drug Metab. Toxicol.
Antibodies to the surface of halothane-altered rabbit hepatocytes in patients with severe halothane-associated hepatitis
N. Engl. J. Med.
Disposition and metabolism of the new oral antidiabetic drug troglitazone in rats, mice and dogs
Arzneimittelforschung
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.
Metabolic activation of troglitazone: identification of a reactive metabolite and mechanisms involved
Drug Metab. Dispos.
Covelent adducts in human primary hepatocytes cultured with ª14C]troglitazone
Drug Metab. Rev.
Troglitazone thiol adduct formation in human liver microsomes: enzyme kinetics and reaction phenotyping
Drug Metab. Lett.
Troglitazone increases cytochrome P-450 3A protein and activity in primary cultures of human hepatocytes
Drug Metab. Dispos.
Effect of troglitazone on cytochrome P450 enzymes in primary cultures of human and rat hepatocytes
Xenobiotica
Effect of troglitazone on the pharmacokinetics of an oral contraceptive agent
J. Clin. Pharmacol.
Rezulin (troglitazone) greatly increases cyclosporine metabolism
J. Heart Lung Transplant.
Troglitazone, a new antidiabetic agent, decreases cyclosporine level
J. Heart Lung Transplant.
Effect of troglitazone on urinary excretion of 6β-hydroxycortisol
J. Clin. Pharmacol.
A study to survey susceptible genetic factors responsible for troglitazone-associated hepatotoxicity in Japanese patients with type 2 diabetes mellitus
Clin. Pharmacol. Ther.
Glutathione S-transferase m1 and t1 null genotypes increase susceptibility to idiosyncratic drug-induced liver injury
Hepatology
Direct and rapid genotyping of glutathione-S-transferase M1 and T1 from human blood specimens using the SmartAmp2 method
Drug Metab. Dispos.
Medical genetics: a marker for Stevens-Johnson syndrome
Nature
HLAB*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol
Proc. Natl. Acad. Sci. U.S.A.
Cited by (35)
Liver organoid as a 3D in vitro model for drug validation and toxicity assessment
2021, Pharmacological ResearchCitation Excerpt :Primary hepatocyte- and pluripotent stem cell-derived organoids were treated with troglitazone for 48 h to a week, a decrease in cellular ATP and glutathione content and increased intracellular lipid accumulation were observed, symptomatic of liver injury and steatosis [68,74,93]. These observations were in concordance with reported studies of troglitazone-induced liver injury [91,93]. Despite the many advantages, organoids are not extensive models and do not take into consideration extrahepatic functions.
Human plasma concentration-time profiles of troglitazone and troglitazone sulfate simulated by in vivo experiments with chimeric mice with humanized livers and semi-physiological pharmacokinetic modeling
2020, Drug Metabolism and PharmacokineticsCitation Excerpt :Troglitazone was a thiazolidinedione class insulin-sensitizing drug for the treatment of type 2 non-insulin-dependent diabetes mellitus, but it was withdrawn from the market in 2000 due to idiosyncratic drug-induced liver injury [14]. During and after the troglitazone case (1997–2000), various side effect prevention strategies were developed and implemented in the pharmaceutical industries [15]. The zone classification system is one of the promising strategies that effectively assess the possible cause of idiosyncratic hepatotoxicity, e.g. formation of reactive metabolites and modification of hepatocellular proteins followed by adaptive immune responses against the modified proteins [16].
Inhibition of mitochondrial fatty acid oxidation in drug-induced hepatic steatosis
2019, Liver ResearchCitation Excerpt :Finally, troglitazone-induced mitochondrial impairment might be reinforced by a reduction of mitochondrial GSH levels, possibly due to lower GSH import into mitochondria.160 Troglitazone can be metabolized into several highly reactive metabolites by different hepatic CYPs including CYP3A4, CYP2C8 and CYP2C19.141,142 In particular, these CYPs generate a quinone and a quinone epoxide derivatives.141,161
Drug-induced liver injury in obesity and nonalcoholic fatty liver disease
2019, Advances in PharmacologyImaging in Gastroenterology
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