Idiosyncratic toxicity: Mechanistic insights gained from analysis of prior compounds

Current Opinion in Drug Discovery and Development

Volumn 8, Issue 1, 2005, Pages 59-65

  Waring, Jeffrey F ^a   Anderson, Mark G ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Hapten hypothesis; Hepatotoxicity; Idiosyncratic drug response; Microarray; Mitochondrial toxicity; Reactive metabolites

Indexed keywords

ABACAVIR; ALLOPURINOL; ANTICONVULSIVE AGENT; ANTIINFECTIVE AGENT; BENOXAPROFEN; BROMFENAC; CARBAMAZEPINE; CYTOCHROME P450 2D6; DICLOFENAC; FELBAMATE; HYPOCHOLESTEROLEMIC AGENT; INSULIN SENSITIZING AGENT; IPRONIAZID; LAMOTRIGINE; LEFLUNOMIDE; NEFAZODONE; NEVIRAPINE; PEMOLINE; PENICILLAMINE; RANITIDINE; STATINE DERIVATIVE; STAVUDINE; TEMAFLOXACIN; TIENILIC ACID; TOLCAPONE; TROGLITAZONE; TROVAFLOXACIN; UNINDEXED DRUG; VALDECOXIB; VALPROATE SEMISODIUM; DRUG;

ATTENTION DEFICIT DISORDER; DEPRESSION; DIABETES MELLITUS; DRUG APPROVAL; DRUG INDICATION; DRUG MARKETING; DRUG METABOLISM; DRUG RESPONSE; DRUG SCREENING; DRUG TOXICITY; ENZYME REGULATION; EPILEPSY; GENETIC POLYMORPHISM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERURICEMIA; IDIOSYNCRATIC DRUG TOXICITY; IMMUNE RESPONSE; IMMUNOPATHOGENESIS; INFLAMMATION; LIVER TOXICITY; MITOCHONDRIAL TOXICITY; NONHUMAN; PAIN; PARKINSON DISEASE; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; TOXICITY TESTING; ULCER; ANIMAL; DRUG DESIGN; GENETICS; METHODOLOGY; TOXICOLOGY;

ANIMALS; DRUG DESIGN; HUMANS; PHARMACEUTICAL PREPARATIONS; POLYMORPHISM, GENETIC; TOXICOLOGY;

EID: 12244311205     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (49)

1. Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, Lilly P, Sanders J, Sipes G, Bracken W, Dorato M et al: Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol (2000) 32(1):56-67.
2. Knowles SR, Uetrecht J, Shear NH: Idiosyncratic drug reactions: The reactive metabolite syndrome. Lancet (2000) 356(9241):1587-1591.
3. Park BK, Kitteringham NR, Powell H, Pirmohamed M: Advances in molecular toxicology - towards understanding idiosyncratic drug toxicity. Toxicology (2000) 153(1-3):39-60.
4. Uetrecht J: Prediction of a new drug's potential to cause idiosyncratic reactions. Curr Opin Drug Discovery Dev (2001) 4(1):55-59. This paper suggests that by designing drugs that work at low doses, IDRs can be avoided.
5. Williams DP, Park BK: Idiosyncratic toxicity: The role of toxicophores and bioactivation. Drug Disc Today (2003) 8(22):1044-1050. Discusses the role of reactive metabolites and puts forth a solution to screen against them.
6. Park BK, Naisbitt DJ, Gordon SF, Kitteringham NR, Pirmohamed M: Metabolic activation in drug allergies. Toxicology (2001) 158(1-2):11-23.
7. Ulrich RG, Bacon JA, Brass EP, Cramer CT, Petrella DK, Sun EL: Metabolic, idiosyncratic toxicity of drugs: Overview of the hepatic toxicity induced by the anxiolytic, panadiplon. Chem Biol Interact (2001) 134(3):251-270.
8. Boelsterli UA: Diclofenac-induced liver injury: A paradigm of idiosyncratic drug toxicity. Toxicol Appl Phamacol (2003) 192(3):307-322.
9. Luyendyk JP, Maddox JF, Cosma GN, Ganey PE, Cockerell GL, Roth RA: Ranitidine treatment during a modest inflammatory response precipitates idiosyncrasy-like liver injury in rats. J Pharmacol Exp Ther (2003) 307(1):9-16. One of several examples in which toxicity is potentiated by LPS-treatment.
10. Roth RA, Luyendyk JA, Maddox JF, Ganey PE: Inflammation and drug idiosyncrasy - is there a connection? J Pharmacol Exp Ther (2003) 307(1):1-8. Provides evidence for a model in which IDRs are caused by episodic changes that predispose the patient to a susceptibility to toxicities under conditions that are normally non-toxic.
11. Masubuchi Y, Nakayama S, Horie T: Role of mitochondrial permeability transition in diclofenac-induced hepatocyte injury in rats. Hepatology (2002) 35(3):544-551.
12. Vermes A, Vermes I: Genetic polymorphisms in cytochrome P450 enzymes: Effect on efficacy and tolerability of HMG-CoA reductase inhibitors. Am J Cardiovasc Drugs (2004) 4(4):247-255.
13. Martin AM, Nolan D, Gaudieri S, Almeida CA, Nolan R, James I, Carvalho F, Phillips E, Christiansen FT, Purcell AW, McCluskey J et al: Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proc Natl Acad Sci USA (2004) 101(12):4180-4185.
14. Yamamoto Y, Yamazaki H, Ikeda T, Watanabe T, Iwabuchi H, Nakajima M, Yokoi T: Formation of a novel quinone epoxide metabolite of troglitazone with cytotoxicity to HepG2 cells. Drug Metab Dispos (2002) 30(2):155-160.
15. Thompson CD, Kinter MT, Macdonald TL: Synthesis and in vitro reactivity of 3-carbamoyl-2-phenylpropionaldehyde and 2-phenylpropenal: Putative reactive metabolites of felbamate. Chem Res Toxicol (1996) 9(8):1225-1229.
16. Dieckhaus CM, Miller TA, Sofia RD, Macdonald TL: A mechanistic approach to understanding species differences in felbamate bioactivation: Relevance to drug-induced idiosyncratic reactions. Drug Metab Dispos (2000) 28(7):814-822.
17. Uetrecht J: Screening for the potential of a drug candidate to cause idiosyncratic drug reactions. Drug Disc Today (2003) 8(18):832-837.
18. Park BK, Pirmohamed M, Kitteringham NR: Role of drug disposition in drug hypersensitivity: A chemical, molecular and clinical perspective. Chem Res Toxicol (1998) 11(9):969-988. Describes the hapten hypothesis in relation to IDRs and hypersensitivity.
19. Aithal GP, Ramsay L, Daly AK, Sonchit N, Leathart JB, Alexander G, Kenna JG, Caldwell J, Day CP: Hepatic adducts, circulating antibodies and cytokine polymorphisms in patients with diclofenac hepatotoxicity. Hepatology (2004) 39(5):1430-1440. Identifies drug-protein adducts in diclofenac-treated patients.
20. Pohl LR, Pumford NR, Martin JL: Mechanisms, chemical structures and drug metabolism. Eur J Haematol Suppl (1996) 60:98-104.
21. Wang M, Dickinson RG: Bile duct ligation promotes covalent drug-protein adduct formation in plasma but not in liver of rats given zomepirac. Life Sci (2000) 68(5):525-537.
22. Evans DC, Watt AP, Nicoll-Griffith DA, Baillie TA: Drug-protein adducts: An industry perspective on minimizing the potential for drug bioactivation in drug discovery and development. Chem Res Toxicol 2004 17(1):3-16.
23. Buchweitz JP, Ganey PE, Bursian SJ, Roth RA: Underlying endotoxemia augments toxic responses to chlorpromazine: Is there a relationship to drug idiosyncrasy? J Pharmacol Exp Ther (2002) 300(2):460-467.
24. Galati G, Tafazoli S, Sabzevari O, Chan TS, O'Brien PJ: Idiosyncratic NSAID drug-induced oxidative stress. Chem Biol Interact (2002) 142(1-2):25-41.
25. Cantoni L, Valaperta R, Ponsoda X, Castell JV, Barelli D, Rizzardini M, Mangolini A, Hauri L, Villa P: Induction of hepatic heme oxygenase-1 by diclofenac in rodents: Role of oxidative stress and cytochrome P-450 activity. J Hepatol (2003) 38(6):776-783.
26. Tirmenstein MA, Hu CX, Gales TL, Maleeff BE, Narayanan PK, Kurali E, Hart TK, Thomas HC, Schwartz LW: Effects of troglitazone on HepG2 viability and mitochondrial function. Toxicol Sci (2002) 69(1):131-138. Demonstrates the effects of troglitazone on mitochondrial permeability transition and cell death.
27. Liguori MJ, Anderson MG, Bukofzer S, McKim J, Pregenzer J, Relief J, Spear BB, Waring JF: Microarray analysis in human hepatocytes suggest a mechanism for hepatotoxicity induced by trovafloxacin. Hepatology (2004): in press. Compares the RNA expression patterns from related quinoione compounds and identifies unique expression in the IDR-inducing compound, trovafloxacin.
28. Eura Y, Ishihara N, Yokota S, Mihara K: Two mitofusin proteins, mammalian homologues of FZO, with distinct functions are both required for mitochondrial fusion. J Biochem (Tokyo) (2003) 134(3):333-344.
29. Santel A, Frank S, Gaume B, Herrler M, Youle RJ, Fuller MT: Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J Cell Sci (2003) 116(Pt13):2763-2774.
30. Anderson VE, Osheroff N: Type II topoisomerases as targets for quinolone antibacterials: Turning Dr Jekyll into Mr Hyde. Curr Pharm Des (2001) 7(5):337-353.
31. Sissi C, Palumbo M: The quinolone family: From antibacterial to anticancer agents. Curr Med Chem Anticancer Agents (2003) 3(6):439-450.
32. Mondal N, Parvin JD: DNA topoisomerase IIα is required for RNA polymerase II transcription on chromatin templates. Nature (2001) 413(6854):435-438.
33. Mondal N, Zhang Y, Jonsson Z, Dhar SK, Kannapiran M, Parvin JD: Elongation by RNA polymerase II on chromatin templates requires topoisomerase activity. Nucleic Acids Res (2003) 31(17):5016-5024.
34. Chen YH, Layne MD, Chung SW, Ejima K, Baron RM, Yet SF, Perrella MA: Elk-3 is a transcriptional represser of nitric-oxide synthase 2. J Biol Chem (2003) 278(41):39572-39577.
35. Shenton JM, Teranishi M, Abu-Asab MS, Yager JA, Uetrecht JP: Characterization of a potential animal model of an idiosyncratic drug reaction: Nevlrapine-induced skin rash in the rat. Chem Res Toxicol (2003) 16(9):1078-1089. Describes an animal model for IDRs.
36. Massen MJ, Uetrecht JP: Tolerance induced by low dose D-penicillamine in the Brown Norway rat model of drug-induced autoimmunity is immune-mediated. Chem Res Toxicol (2004) 17(1):82-94.
37. Bourdi M, Masubuchi Y, Reilly TP, Amouzadeh HR, Martin JL, George JW, Shah AG, Pohl LR: Protection against acetaminophen-induced liver injury and lethality by interleukin 10: Role of inducible nitric oxide synthase. Hepatology (2002) 35(2):289-298.
38. Gardner CR, Laskin JD, Dambach DM, Sacco M, Durnam SK, Bruno MK, Cohen SD, Gordon MK, Gerecke DR, Zhou P, Laskn DL: Reduced hepatotoxicity of acetaminophen in mice lacking inducible nitric oxide synthase: Potential role of tumor necrosis factor-α and interleukin-10. Toxicol Appl Pharmacol (2002) 184(1):27-36.
39. Gardner CR, Laskin JD, Dambach DM, Chiu H, Durham SK, Zhou P, Bruno M, Gerecke DR, Gordon MK, Laskin DL. Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1. Potential role of inflammatory mediators. Toxicol Appl Pharmacol (2003) 192(2):119-130.
40. Masubuchi Y, Bourdi M, Reilly TP, Graf ML, George JW, Pohl LR: Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease. Biochem Biophys Res Commun (2003) 304(1):207-212.
41. Lloyd S, Hayden MJ, Sakai Y, Fackett A, Silber PM, Hewitt NJ, Li AP: Differential in vitro hepatotoxicity of troglitazone and rosiglitazone among cryopreserved human hepatocytes from 37 donors. Chem Biol Interact (2002) 142(1-2):57-71.
42. Hewitt NJ, Lloyd S, Hayden M, Butler R, Sakai Y, Springer R, Fackett A, Li AP: Correlation between troglitazone cytotoxicity and drug metabolic enzyme activities in cryopreserved human hepatocytes. Chem Biol Interact (2002) 142(1-2):73-82.
43. Harrigan GG, LaPlante RH, Cosma GN, Cockerell G, Goodacre R, Maddox JF, Luyendyk JP, Ganey PE, Roth RA: Application of high-throughput Fourier-transform infrared spectroscopy in toxicology studies: Contribution to a study on the development of an animal model for idiosyncratic toxicity. Toxicol Lett (2004) 146(3):197-205.
44. Watanabe I, Tomita A, Shimizu M, Sugawara M, Yasumo H, Koishi R, Takahashi T, Miyoshi K, Nakamura K, Izumi T, Matsushita Y et al: A study to survey susceptible genetic factors responsible for troglitazone-associated hepatotoxicity in Japanese patients with type 2 diabetes mellitus. Clin Pharmacol Ther(2003) 73(5):435-455.
45. Bulera SJ, Theiss JC, Festerling TA, de la Iglesia FA: In vitro photogenotoxic activity of clinafloxacin: A paradigm predicting photocarcinogenicity. Toxicol Applied Pharmacol (1999) 156(3):222-230.
46. Waring JF, Jolly RA, Ciurlionis R, Lum PY, Praestgaard JT, Morfitt DC, Buratto B, Roberts C, Schadt E, Ulrich RG: Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles. Toxicol Appl Pharmacol (2001) 175(1):28-42.
47. Waring JF, Ciurlionis R, Jolly RA, Heindel M, Ulrich RG: Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity. Toxicol Lett (2001) 120(1-3):359-368.
48. Kier LD, Neft R, Tang L, Suizu R, Cook T, Onsurez K, Tiegler K, Sakai Y, Ortiz M, Nolan T, Sankar U et al: Applications of microarrays with toxicologically relevant genes (tox genes) for the evaluation of chemical toxicants in Sprague Dawley rats in vivo and human hepatocytes in vitro. Mutat Res (2004) 549(1-2):101-113. One of the first papers to apply microarray technology to idiosyncratic toxicity.
49. Li AP: A review of the common properties of drugs with idiosyncratic hepatotoxicity and the 'multiple determinant hypothesis' for the manifestation of idiosyncratic drug toxicity, Chem Biol Interact (2002) 142(1-2):7-23 Describes how multiple factors can combine to contribute to IDRs.