Role of metabolism in drug-induced idiosyncratic hepatotoxicity

Critical Reviews in Toxicology

Volumn 35, Issue 4, 2005, Pages 325-361

  Walgren, Jennie L ^a   Mitchell, Michael D ^a   Thompson, David C ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(3 CHLOROPHENYL)PIPERAZINE; 1 OCTYLIMIDAZOLE; 2 HYDROXYCARBAMAZEPINE; 2 HYDROXYIMINOSTILBENE; 2 PHENYLPROPENAL; 3 METHYLCHOLANTHRENE; 4 HYDROXYCATECHOL; 4 HYDROXYTAMOXIFEN; ABACAVIR; ACETOHYDRAZIDE; ACETYLISONIAZID; ACROLEIN DERIVATIVE; ALPHA NAPHTHOFLAVONE; ALPIDEM; AMINEPTINE; AMINODANTROLENE; AMINOTRANSFERASE; AMODIAQUINE; ANILINE DERIVATIVE; BENOXAPROFEN; BOSENTAN; BROMFENAC; CALICHEAMICIN; CARBAMAZEPINE; CARBAMIC ACID; CARBOXYLIC ACID DERIVATIVE; CARBROMAL; CATECHOL DERIVATIVE; CHLORPROMAZINE; CINCHOPHEN; CLOPIDOGREL; CLOZAPINE; COBALT CHLORIDE; CYTOCHROME P450; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A; CYTOCHROME P450 3A4; DACARBAZINE; DANTROLENE; DESFLURANE; DICLOFENAC; DICLOFENAC POTASSIUM; DIDANOSINE; DIETHYLDITHIOCARBAMIC ACID; DIHYDRALAZINE; DILEVALOL; DIMETHYLANILINE MONOOXYGENASE; DISULFIRAM; DRUG METABOLITE; EBROTIDINE; ENFLURANE; EPOXIDE; ETRETIN; ETRETINATE; FAMOTIDINE; FELBAMATE; FIALURIDINE; FLUCONAZOLE; FLUTAMIDE; GEMTUZUMAB OZOGAMICIN; GLAFENINE; GLUCURONIDE; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 1A3; GLUCURONOSYLTRANSFERASE 1A9; GLUTATHIONE; GLUTATHIONE DISULFIDE; HALOTHANE; HYDRAZINE; HYDRAZINE DERIVATIVE; HYDROXYCARBOXYLIC ACID; HYDROXYFLUTAMIDE; HYDROXYNEFAZODONE; IBUFENAC; IMIDAZOLE DERIVATIVE; IMINE; IPRONIAZID; ISAXONINE; ISAXONINE PHOSPHATE; ISOFLURANE; ISONIAZID; ISOPROPYLHYDRAZINE; KETOCONAZOLE; LABETALOL; LAMIVUDINE; LEFLUNOMIDE; LEVODOPA; LIPOPOLYSACCHARIDE; LIVER ENZYME; MANDELIC ACID; METHOTREXATE; METHYLDOPA; METYRAPONE; N DEACETYL KETOCONAZOLE; NALTREXONE; NEFAZODONE; NEVIRAPINE; NIPEROTIDINE; NONSTEROID ANTIINFLAMMATORY AGENT; OCTYLAMINE; OPHTHAZIN; OXANDROLONE; OXAZOLIDINONE DERIVATIVE; OXYMETHOLONE; PARACETAMOL; PEMOLINE; PEMOLINE MAGNESIUM; PERHEXILINE MALEATE; PHENOBARBITAL; PIOGLITAZONE; PIPERONYL BUTOXIDE; PIRPROFEN; PROADIFEN; RANITIDINE; RIFAMPICIN; RNA DIRECTED DNA POLYMERASE INHIBITOR; ROSIGLITAZONE; STAVUDINE; STILBENE DERIVATIVE; TACLEER; TACRINE; TAMOXIFEN; TAMOXIFEN CITRATE; TENOFOVIR; TENOFOVIR DISOPROXIL; TERBINAFINE; THIAMAZOLE; TIANEPTINE; TICLOPIDINE; TIENILIC ACID; TILBROQUINOL; TILIQUINOL; TOLCAPONE; TOREMIFENE; TRIFLUOROMETHYLANILINE; TROGLITAZONE; TROVAFLOXACIN; UNCLASSIFIED DRUG; VALPROIC ACID; ZALCITABINE; ZIDOVUDINE; ZILEUTON;

ACUTE GRANULOCYTIC LEUKEMIA; AGRANULOCYTOSIS; ALCOHOL LIVER CIRRHOSIS; ALCOHOL LIVER DISEASE; ALCOHOLISM; ALZHEIMER DISEASE; AMEBIASIS; AMINOTRANSFERASE BLOOD LEVEL; ANAPHYLAXIS; APLASTIC ANEMIA; ASTHMA; BIRTH DEFECT; BRAIN PSEUDOTUMOR; BREAST CANCER; BREATHING DISORDER; CHOLESTATIC HEPATITIS; CHRONIC LIVER DISEASE; CLINICAL TRIAL; COMA; COVALENT BOND; CYANOSIS; CYTOTOXICITY; DEATH; DNA METHYLATION; DOSE RESPONSE; DRUG ACTIVATION; DRUG ACTIVITY; DRUG ANTAGONISM; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INDUCED DISEASE; DRUG INHIBITION; DRUG MECHANISM; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG STRUCTURE; DRUG WITHDRAWAL; ENDOMETRIUM CANCER; ENZYME BLOOD LEVEL; EOSINOPHILIA; EPILEPSY; FATTY LIVER; FEVER; GOUT; HALOTHANE LIVER INJURY; HAPTEN CARRIER COMPLEX; HEMATOLOGIC DISEASE; HEPATITIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERACTIVITY; HYPERSENSITIVITY REACTION; HYPERTENSION; INCIDENCE; LACTIC ACIDOSIS; LIPIDOSIS; LIVER CARCINOGENESIS; LIVER DISEASE; LIVER FAILURE; LIVER INJURY; LIVER MICROSOME; LIVER NECROSIS; LIVER TOXICITY; LIVER VENOOCCLUSIVE DISEASE; LUPUS VULGARIS; LYMPHOMA; MALIGNANT HYPERTHERMIA; MELANOMA; METABOLIC ACTIVATION; MYOCARDITIS; NECROSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBSTRUCTIVE JAUNDICE; OCCUPATIONAL EXPOSURE; OPIATE ADDICTION; ORTHOSTATIC HYPOTENSION; PANCREATITIS; PARKINSONISM; PELIOSIS HEPATIS; PERIPHERAL NEUROPATHY; PROSTATE CANCER; PROTEIN EXPRESSION; PSORIASIS; PULMONARY HYPERTENSION; RASH; REVIEW; SEIZURE; TERATOGENICITY; TUBERCULOSIS;

ANIMALS; HEPATITIS, TOXIC; HUMANS; PHARMACEUTICAL PREPARATIONS;

EID: 18844373318     PISSN: 10408444     EISSN: None     Source Type: Journal    
DOI: 10.1080/10408440590935620     Document Type: Review

References (259)

1. Adams, L., Jeffrey, F.P., Deboer, B., and Garas, G. (2002). Ticlopidine-associated cholestatic hepatitis. Int. Med. J. 32:359-360.
2. Alden, C., Lin, J., and Smith, P. (2003). Predictive toxicology technology for avoiding idiosyncratic liver injury. Preclinica May/June, 27-35.
3. Alvir, J.M., and Lieberman, J.A. (1994). Agranulocytosis: Incidence and risk factors. J. Clin. Psychiatry 55(Suppl B):137-138.
4. Andrade, R.J., Lucena, M.I., Martin-Vivaldi, R., Fernandez, M.C., Nogueras, F., Pelaez, G., Gomez-Outes, A., Garcia-Escano, M.D., Bellot, V., Hervas, A., Cardenas, F., Bermudez, F., Romero, M., and Sameron, J. (1999). Acute liver injury associated with the use of ebrotidine, a new H2-receptor antagonist. J. Hepatol. 31:641-646.
5. Arnold, T.H, Jr, Epps, J.M. 3rd, Cook, H.R., and Hamrick, M.E. (1983). Dantrolene sodium: Urinary metabolites and hepatotoxicity. Res. Commun. Chem. Pathol. Pharmacol. 39:381-398.
6. Asbury, R.F., Rosenthal, S.N., Descalzi, M.E., Ratcliffe, R.L., and Arseneau, J.C. (1980). Hepatic veno-occlusive disease due to DTIC. Cancer 45:2670-2674.
7. Askmark, H., and Wiholm, B. (1990). Epidemiology of adverse reactions to carbamazepine as seen in a spontaneous reporting system. Acta Neurol. Scand. 81:131-140.
8. Ayrton, A.D., Ioannides, C., and Parke, D.V. (1991). Induction of the cytochrome P450 I and IV families and peroxisomal proliferation in the liver of rats treated with benoxaprofen. Possible implications in its hepatotoxicity. Biochem. Pharmacol. 42:109-115.
9. Baillie, T.A. (1988). Metabolic activation of valproic acid and drug-mediated hepatotoxicity. Role of the terminal olefin, 2-n-propyl-4- pentenoic acid. Chem. Res. Toxicol. 1:195-199.
10. Ballet, F. (1997). Hepatotoxicity in drug development: Detection, significance and solutions. J. Hepatol. 26(Suppl. 2):26-36.
11. Bartle, W.R., Fisher, M.M., and Kerenyi, N. (1985). Disulfiram-induced hepatitis. Report of two cases and review of the literature. Dig. Dis. Sci. 50:834-837.
12. Baty, V., Denis, B., Goudot, C., Bas, V., Renkes, P., Bigard, M.A., Boissel, P., and Gaucher, P. (1994). Hepatitis induced by alpidem (Ananxyl). Four cases, one of them fatal. Gastroenterol. Clin. Biol. 18:1129-1131.
13. Baud, F., Bernuau, J., Benmami, N., Pariente, E.A., Bouygues, M., Guillan, J., Roche-Sicot, J., Degott, C., Rueff, B., Pessayre, D., and Benhamou, J.P. (1983). Acute hepatitis caused by isaxonine phosphate (Nerfactor). Gastroenterol. Clin. Biol. 7:352-354.
14. Berson, A., Descatoire, V., Sutton, A., Fau, D., Maulny, B., Vadrot, N., Feldmann, G., Berthon, B., Tordjmann, T., and Pessayre, D. (2001). Toxicity of alpidem, a peripheral benzodiazepine receptor ligand, but not zolpidem, in rat hepatocytes: Role of mitochondrial permeability transition and metabolic activation. J. Pharmacol. Exp. Ther. 299:793-800.
15. Berson, A., Wolf, C., Chachaty, C., Fisch, C., Fau, D., Eugene, D., Loeper, J., Gauthier, J.C., Beaune, P., Pompon, D., Maurel, P., and Pessayre, D. (1993). Metabolic activation of the nitroaromatic antiandrogen flutamide by rat and human cytochrome P-450, including forms belonging to the 3A and 1A subfamilies. J. Pharmacol. Exp. Ther. 265:366-372.
16. Bertino, J., and Fish, D. (2000). The safety profile of the fluoroquinolones. Clin. Ther. 22:798-817.
17. Bhogaraju, A., Nazeer, S., Al-Gaghdadi, Y., Rahman, M., Wrestler, F., and Patel, N. (1999). Diclofenac-associated hepatitis. Southern Med. J. 92:711-713.
18. Black, M., Mitchell, J.R., Zimmerman, H.J., Ishak, K.G., and Epler, G.R. (1975). Isoniazid-associated hepatitis in 114 patients. Gastroenterology 69:289-302.
19. Blum, M.D., and Graham, D.J. (1994). Temafloxacin syndrome: Review of 95 cases. Clin. Infect. Dis. 18:946-950.
20. Boelsterli, U.A. (2002). Xenobiotic acyl glucuronides and acyl CoA thioesters as protein-reactive metabolites with the potential to cause idiosyncratic drug reactions. Curr. Drug Metab. 3:439-450.
21. Boelsterli, U.A., Zimmerman, H.J., and Kretz-Rommel, A. (1995). Idiosyncratic liver toxicity of nonsteroidal anti-inflammatory drugs: Molecular mechanisms and pathology. Crit. Rev. Toxicol. 25:207-235.
22. Bolt, H.M., and Remmer, H. (1976). Implication of rifampicin-quinone in the irreversible binding of rifampicin to macromolecules. Xenobiotica 6:21-32.
23. Bolton, J.L., Comeau, E., and Vukomanovic, V. (1995). The influence of 4-alkylsubstituents on the formation and reactivit of 2-methoxyquinone methides: Evidence that extended π-conjugation dramatically stabilized the quinone methide formed from eugenol. Chem.-Biol. Interact. 95:279-290.
24. Bonierbale, E., Valadon, P., Pons, C., Desfosses, B., Dansette, P.M., and Mansuy, D. (1999). Opposite behaviors of reactive metabolites of tienilic acid and its isomer toward liver proteins: Use of specific antitienilic acid-protein adduct antibodies and the possible relationship with different hepatotoxic effect of the two compounds. Chem. Res. Toxicol. 12:286-296.
25. Bonkovsky, H.L., Azar, R., Bird, S., Szabo, G., and Banner, B. (2002). Severe cholestatic hepatitis caused by thiazolidinediones: Risks associated with substituting rosiglitazone for troglitazone. Dig. Dis. Sci. 47:1632-1637.
26. Bourdi, M., Larrey, D., Nataf, J., Bernuau, J., Pessayre, D., Iwasaki, M., Guengerich, F.P., and Beaune, P.H. (1990) Anti-liver endoplasmic reticulum autoantibodies are directed against human cytochrome P-450IA2. A specific marker of dihydralazine-induced hepatitis. J. Clin. Invest. 85:1967-1973.
27. Bourdi, M., Tinel, M., Beaune, P.H., and Pessayre, D. (1994). Interactions of dihydralazine with cytochromes P4501A: A possible explanation for the appearance of anti-cytochrome P4501A2 autoantibodies. Mol. Pharmacol. 45:1287-1295.
28. Breyer-Pfaff, U., and Nill, K. (2004). Carbonyl reduction of naltrexone and dolasetron by oxidoreductases isolated from human liver cytosol. J. Pharm. Pharmacol. 56:1601-1606.
29. Buchweitz, J.P., Ganey, P.E., Bursian, S.J., and Roth, R.A. (2002). Underlying endotoxemia augments toxic responses to chlorpromazine: Is there a relationship to drug idiosyncrasy? J. Pharmacol. Exp. Ther. 300:460-467.
30. Caldwell, J., Fakurazi, S., Ramsay, L.A., Somchit, N., and Goldin, R.D. (2000). Benoxaprofen forms protein adducts in the bile canaliculi of female CD1 mice. Toxicol. Sci. 54(Suppl. 1):46 (Abstract).
31. Castillo, J.R., Torello, J., and Hernandez, A. (2000). Liver injury caused by ebrotidine: A new example of the utility of the postmarketing surveillance. Eur. J. Clin. Pharmacol. 56:187-189.
32. Castillo, M., and Smith, P.C. (1995). Disposition and reactivity of ibuprofen and ibufenac acyl glucuronides in vivo in the rhesus monkey and in vitro with human serum albumin. Drug Metab. Dispos. 23:566-572.
33. Cattelan, A.M., Erne, E., Salatino, A., Trevenzoli, M., Carretta, G., Meneghetti, F., and Cadrobbi, P. (1999). Severe hepatic failure related to nevirapine treatment. Clin. Infect. Dis. 29:455-456.
34. Chase, R.E., Holaday, D.A., Fiserove-Bergerova, V., Saidman, L.J., and Mack, F.E. (1971). The biotransformation of ethrane in man. Anesthesiology 35:262-267.
35. Christie, G., Breckenridge, A.M., and Park, B.K. (1989). Drug-protein conjugates-XVIII. Detection of antibodies towards the antimalarial amodiaquine and its quinone imine metabolite in man and the rat. Biochem. Pharmacol. 38:1451-1458.
36. Clark, J.A., Zimmerman, H.J., and Tanner, L.A. (1990). Labetolol hepatotoxicity. Ann. Intern. Med. 113:210-213.
37. Cohen, E.N., Trudell, J.R., Edwards, H.D., and Watson, D. (1975). Urinary metabolites of halothane in man. Anesthesiology 43:392-401.
38. Cooper, R.G., Evans, D.A.P., and Whibley, E.J. (1984). Polymorphic hydroxylation of perhexiline maleate in man. J. Med. Genet. 21:27-33.
39. Cui, L., Yoon, S., Schinazi, R.F., and Sommadossi, J.-P. (1995). Cellullar and molecular events leading to mitochondrial toxicity of 1-(2-deoxy-2-fluoro-1-β-D-arabinofuranosyl)-5-iodouracil in human liver cells. J. Clin. Invest. 95:555-563.
40. Cuthbert, M.F. (1974). Adverse reactions to non-steroidal antirheumatic drugs. Curr. Med. Res. Opin. 2:600-610.
41. Cutrin, P.C., Nieto, P.E., Batalla, E.A., Casal, I.L., Perez, B.E., and Lorenzo, Zuniga V. (1991). Toxic hepatitis from cinchophen: Report of 3 cases. Med Clin (Barc) 97:104-106.
42. Dahlin, D.C., and Nelson, S.D. (1982). Synthesis, decomposition kinetics, and preliminary toxicological studies of pure N-acetyl-p-benzoquinone imine, a proposed toxic metabolite of acetaminophen. J. Med. Chem. 25:885-886.
43. Dahms, M., and Spahn-Langguth, H. (1996). Covalent binding of acidic drugs via reactive metabolites: Detection of benoxaprofen and flunoxaprofen protein adducts in biological material. Pharmazie 51:874-881.
44. Danan, G., Homberg, J.C., Bernuau, J., Roche-Sicot, J., and Pessayre, D. (1983). Iproniazid-induced hepatitis. The diagnostic value of a new antimitochondrial antibody anti-M6. Gastroenterol. Clin. Biol. 7:529-532.
45. Dasaradhi, L., and Shibutami, S. (1997). Identification of tamoxifen-DNA adducts formed by α-sulfate tamoxifen and α-acetoxytamoxifen. Chem. Res. Toxicol. 10:189-196.
46. Dehal, S.S., and Kupfer, D. (1996). Evidence that the catechol 3,4-dihydroxytamoxifen is a proximate intermediate to the reactive species binding covalently to proteins. Cancer Res. 56:1283-1290.
47. Dehal, S.S., and Kupfer, D. (1999). Cytochrome P-450 3A and 2D6 catalyze ortho hydroxylation of 4-hydroxytamoxifen and 3-hydroxytamoxifen (droloxifene) yielding tamoxifen catechol: Involvement of catechols in covalent binding to hepatic proteins. Drug Metab. Dispos. 27:681-688.
48. Depla, A.C., Vermeersch, P.H., van Gorp, L.H., and Nadorp, J.H. (1990). Fatal acute liver failure associated with pirprofen. Report of a case and review of the literature. Neth. J. Med. 37:23-36.
49. Dieckhaus, C.M., Miller, T.A., Sofia, R.D., and Macdonald, T.L. (2000). A mechanistic approach to understanding species differences in felbamate bioactivation: Relevance to drug-induced idiosyncratic reactions. Drug Metab. Dispos. 28:814-822.
50. Dieckhaus, C.M., Santos, W.L., Sofia, R.D., and Macdonald, T.L. (2001). The chemistry, toxicology, and identification in rat and human urine of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one: A reactive metabolite in felbamate bioactivation. Chem. Res. Toxicol. 14:958-964.
51. Dieckhaus, C.M., Thompson, C.D., Roller, S.G., and Macdonald, T.L. (2002). Mechanisms of idiosyncratic drug reactions: The case of felbamate. Chem.-Biol. Interact. 142:99-117.
52. Dreifuss, F.E., Santilli, N., Langer, D.H., Sweeney, K.P., Moline, K.A., and Menander, K.B. (1987). Valproic acid hepatic fatalities: A retrospective review. Neurology 37:379-385.
53. Durand, A., Thenot, J.P., Bianchetti, G., and Morselli, P.L. (1992). Comparative pharmacokinetic profile of two imidazopyridine drugs: Zolpidem and alpidem. Drug Metab. Rev. 24:239-266.
54. Durham, J.A., Gandolfi, A.J., and Bentley, J.B. (1984). Hepatotoxicological evaluation of dantrolene sodium. Drug Chem. Toxicol. 7:23-40.
55. Dybing, E., Nelson, S.D., Mitchell, J.R., Sasame, H.A., and Gillette, J.R. (1976). Oxidation of α-methyldopa and other catechols by cytochrome p-450-generated superoxide anion: Possible mechanism of methyldopa hepatitis. Mol. Pharmacol. 12:911-920.
56. Egger, H., Bartlett, F., Yuan, H.P., and Karliner, J. (1982). Metabolism of pirprofen in man, monkey, rat and mouse. Drug Metab. Dispos. 10:529-536.
57. Eliasson, E., Stal, P., Oksanen, A., and Lytton, S. (1998). Expression of autoantibodies to specific cytochromes p450 in a case of disulfiram hepatitis. J. Hepatol. 29:819-825.
58. EMEA (European Medicines Evaluation Agency), Committee for Proprietary Medicinal Products (CPMP/1694/99), Scientific Discussion, accessed at www.eudra.org/humandocs/PDFs/EPAR/Arava/169499en6%20.pdf, 2000.
59. Erve, J.C.L., Jensen, O.N., Valentine, H.S., Amarnath, V., and Valentine, W.M. (2000). Disulfiram generates a stable N,N-diethylcarbamoyl adduct on Cys-125 of rat hemoglobin β-chains in vivo. Chem. Res. Toxicol. 13:237-244.
60. Evans, D.C., Watt, A.P., Nicoll-Griffith, D.A., and Baillie, T.A. (2004) Drug-protein adducts: An industry perspective on minimizing the potential for drug bioactivation in drug discovery and development. Chem. Res. Toxicol. 17:3-16.
61. Fattinger, K., Funk, C., Pantze, M., Weber, C., Reichen, J., Stieger, B., and Meier, P.J. (2001). The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: A potential mechanism for hepatic adverse reactions. Clin. Pharmacol. Ther. 69:223-231.
62. Fau, D., Eugene, E., Berson, A., Letteron, P., Fromenty, B., Fisch, C., and Pessayre, D. (1994). Toxicity of the antiandrogen flutamide in isolated rat hepatocytes. J. Pharmacol. Exp. Ther. 269:954-962.
63. Fernandes, N.F., Geller, S.A., and Fong, T.-L. (1998). Terbinafine hepatotoxicity: Case report and review of the literature. Am J Gastroenterology 93:459-460.
64. Fichtenbaum, C.J., and Gerber, J.G. (2002). Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection. Clin. Pharmacokinet 41:1195-1211.
65. Fouin-Fortunet, H., Letteron, P., Tinel, M., Degott, C., Flejou, J.F., and Pessayre, D. (1984). Mechanism for isaxonine hepatitis. II. Protective role of glutathione and toxicological studies in mice. J. Pharmacol. Exp. Ther. 229:851-858.
66. Friedman, M.A., Woodcock, J., Lumpkin, M.M., Shuren, J.E., Hass, A.E., and Thompson, L.J. (1999). The safety of newly approved medicines: Do recent market removals mean there is a problem? JAMA 281:1728-1734.
67. Fromenty, B., and Pessayre, D. (1995). Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity. Pharm. Ther. 67:101-154.
68. Fung, M., Thornton, A., Mybeck, K., Wu, J.H., Hornbuckle, K., and Muniz, E. (2001). Evaluation of the characteristics of safety withdrawal of prescription drugs from worldwide pharmaceutical markets - 1960 to 1999. Drug Information J. 35:293-317.
69. Furst, S.M., and Uetrecht, J.P. (1993). Carbamazepine metabolism to a reactive intermediate by the myeloperoxidase system of activated neutrophils. Biochem Pharmacol. 45:1267-1275.
70. Gale, E.A. (2001). Lessons from the glitazones: A story of drug development. Lancet 357:1870-1875.
71. 14C] halothane. J. Pharmacol. Exp. Ther. 214:721-727.
72. Ganey, P.E., and Roth, R.A. (2001). Concurrent inflammation as a determinant of susceptibility to toxicity from xenobiotic agents. Toxicology 28:195-208.
73. Garcia-Pando, A.C., Garcia del Pozo, J., Sanchez, A.S., Martin, A.V., Rueda de Castro, A.M., and Lucena, M.I. (2002). Hepatotoxicity associated with the new antidepressants. J. Clin. Psychiatry 63:135-137.
74. Gardner, I., Leeder, J.S., Chin, T., Zahid, N., and Uetrecht, J.P. (1998). A comparison of the covalent binding of clozapine and olanzapine to human neutrophils in vitro and in vivo. Mol. Pharmacol. 53:999-1008.
75. Gasbarrini, G., Gentiloni, N., Febbraro, S., Gasbarrini, A., Di Campli, C., Cesana, M., Migio, F., Miglioli, M., Ghinelli, F., D'Ambrosi, A., Amoroso, P., Pacini, F., and Salvadori, G. (1997). Acute liver injury related to the use of niperotidine. J. Hepatol. 27:583-586.
76. Gascoigne, E.W., Barton, G.J., Michales, M., Meuldermans, W., and Heykants, J. (1981). The kinetics of ketoconazole in animals and man. Clin. Res. Rev. 1:177-187.
77. Gavish, D., Katz, M., Gottehrer, N., Israeli, A., Lijovetzky, G. and Holubar, K. (1985). Cholestatic jaundice, an unusual side effect of etretinate. J. Am. Acad. Dermatol. 13:669-670.
78. Genéve, J. (1987). Inhibition of mitochondrial beta-oxidation of fatty acids by pirprofen. Role in microvesicular steatosis due to this non-steroidal anti-inflammatory drug. J. Pharmacol. Exp. Ther. 242:1137-1142.
79. Genéve, J., Larrey, D., Amouyal, G., Belghiti, J., and Pessayre, D. (1987). Metabolic activation of the tricyclic antidepressant amineptine by human liver cytochrome p-450. Biochem. Pharmacol. 36:2421-2424.
80. Giles, F.J., Kantarjian, H.M., Kornblau, S.M., Thomas, D.A., Garcia-Manero, G., Waddelow, T.A., David, C.L., Phan, A.T., Colburn, D.E., Rashid, A., and Estey, E.H. (2001). Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Cancer 92:406-413.
81. Goodwin, D.C., Aust, S.D., and Grover, T.A. (1996). Free radicals produced during the oxidation of hydrazines by hypochlorous acid. Chem. Res. Toxicol. 9:1333-1339.
82. Haasio, K., Sopanen, L., Vaalavirta, L., Linden, I.-B., and Heinonen, E.F. (2001). Comparative toxicological study on the hepatic safety of entacapone and tolcapone in the rat. J. Neural Transm. 108:79-91.
83. Haasio, K., Koponen, A., Penttila, K.E., and Nissinen, E. (2002). Effects of entacapone and tolcapone on mitochondrial membrane potential. Eur. J. Pharmacol. 453:21-26.
84. Ha-Duong, N.T., Dijols, S., Macherey, A.C., Goldstein, J.A., Dansette, P.M., and Mansuy, D. (2001). Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P450 2C19. Biochemistry 40:12112-12122.
85. Hard, G.C., Iatropoulos, M.J., Jordan, K., Radi, L., Kaltenberg, O.P., Imondi, A.R., and Williams, G.M. (1993). Major difference in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats. Cancer Res., 53(19):4534-4541.
86. Hargus, S.J., Amouzedeh, H.R., Pumford, N.R., Myers, T.G., McCoy, S.C., and Pohl, L.R. (1994). Metabolic activation and immunochemical localization of liver protein adducts of the nonsteroidal antiinflammatory drug diclofenac. Chem. Res. Toxicol. 7:575-582.
87. Harrison, A.C., Kitteringham, N.R., Clarke, J.B., and Park, B.K. (1992). The mechanism of bioactivation and antigen formation of amodiaquine in the rat. Biochem. Pharmacol. 43:1421-1430.
88. Hart, B.W., and Faiman, M.D. (1992). In vitro and in vivo inhibition of rat liver aldehyde dehydrogenase by S-methyl N,N-diethylthiocarbamate sulfoxide, a new metabolite of disulfiram. Biochem. Pharmacol. 43:403-406.
89. He, K., Woolf, T.F., Kindt, E.K., Fielder, A.E., and Talaat, R.E. (2001). Troglitazone quinone formation catalyzed by human and rat CYP3A: An atypical CYP oxidation reaction. Biochem. Pharmacol. 62:191-198.
90. Heel, R.C., Brogden, R.N., Carmine, A., Morley, P.A., Speight, T.M., and Avery, G.S. (1982). Ketoconazole: A review of its therapeutic efficacy in superficial and systemic fungal infections. Drugs 23:1-36.
91. Hendrickson, H.P., Scott, D.O., and Lunte, C.E. (1989). Identification of 9-hydroxylamine-1,2,3,4-tetrahydroacridine as a hepatic microsomal metabolite of tacrine by high-performance liquid chromatography and electrochemistry. J. Chromatogr. 487:401-408.
92. Hill, D.L. (1975). Microsomal metabolism of triazenyl-imidazoles. Cancer Res. 35:3106-3110.
93. Holaday, D.A., Fiserova-Bergerova, V., Latto, I.P., and Zumbiel, M.A. (1975). Resistance of isoflurane to biotransformation in man. Anesthesiology 43:392-401.
94. Homberg, J.C., Stelly, N., Andreis, I., Abuaf, N., Sadoun, F., and Andre, J. (1982). A new antimitochondria antibody (anti-M6) in iproniazid-induced hepatitis. Clin. Exp. Immunol. 47:93-102.
95. Homberg, J.C., Andre, C., and Abuaf, N. (1984). A new anti-liver kidney microsome antibody (anti-KLM2) in tienilic acid-induced hepatitis. Clin. Exp. Immunol. 55:561-570.
96. Hueper, W.E., Cinchophen (Atophan): A critical review. Medicine 27, 43, 1948.
97. Hummer, M., Kurz, M., Kurzthaler, I., Oberbauer, H., Miller, C., and Fleischhacker, W.W. (1997). Hepatotoxicity of clozapine. J. Clin. Psychopharmacol. 17(4):314-317.
98. Iverson, S.L., and Uetrecht, J.P. (2001). Identification of a reactive metabolite of terbinafine: Insights into terbinafine-induced hepatotoxicity. Chem. Res. Toxicol. 14:175-181.
99. Jarman, M., Poon, G.K., Rowlands, M.G., Grimshaw, R.M., Horton, M.N., Potter, G.A., and McCague, R. (1995). The deuterium isotope effect for the α-hydroxylation of tamoxifen by rat liver microsomes accounts for the reduced genotoxicity of D5-ethyltamoxifen. Carcinogenesis 16:683-688.
100. Jayyosi, Z., Totis, M., Souhaili, H., Goulon-Ginet, C., Livertous, M.H., Batt, A.M., and Siest, G. (1987). Induction of hepatic cytochrome P-450c-dependent monooxygenase activities by dantrolene in rat. Biochem. Pharmacol. 36:2481-2487.
101. Jayyosi, Z., Villoutreix, J., Ziegler, J.M., Batt, A.M., De Maack, F., Siest, G., and Thomas, P.E. (1993). Identification of cytochrome P-450 isozymes involved in the hydroxylation of dantrolene by rat liver microsomes. Drug Metab. Dispos. 21:939-945.
102. Jean, P., Lopez-Garcia, P., Dansette, P., Mansuy, D., and Goldstein, J.L. (1996). Oxidation of tienilic acid by human yeast-expressed cytochrome P-450 2C8, 2C9, 2C18 and 2C19. Evidence that this drug is a mechanism-based inhibitor specific for cytochrome P-450 2C9. Eur. J. Biochem. 241:797-804.
103. Jiang, X., Khursigara, G., and Rubin, R.L. (1994). Transformation of lupus-inducing drugs to cytotoxic products by activated neutrophils. Science 266:801-813.
104. Jin, L., Davis, M.G., Hu, P., and Baillie, T.A. (1994). Identification of novel glutathione conjugates of disulfiram and diethyldithiocarbamate in rat bile by liquid chromatography-tandem mass spectrometry. Evidence for metabolic activation of disulfiram in vivo. Chem. Res. Toxicol. 7:526-533.
105. Johnson, S., Baraboutis, J.G., Sha, B.E., Proia, L.A., and Kessler, H.A. (2000). Adverse effects associated with use of nevirapine in HIV postexposure for 2 health care workers [Letters]. JAMA 284:2722-2723.
106. Jones, R.M., and Lim, C.K. (2002). Toremifene metabolism in rat, mouse and human liver microsomes: Identification of α-hydroxytoremifene by LC-MS. Biomed. Chromatogr. 16:361-363.
107. Jorga, K., Fotteler, B., Heizmann, P., and Gasser, R. (1999). Metabolism and excretion of tolcapone, a novel inhibitor of catechol-O-methyltransferase. Br. J. Clin. Pharmacol. 48:513-520.
108. Joshi, E.M., Heasley, B.H., Chordia, M.D., and Macdonald, T.L. (2004). In vitro metabolism of 2-acetylbenzothiophene: relevance to zileuton hepatoxicity. Chem. Res. Toxicol. 17:137-143.
109. Ju, C. and Uetrecht, J.P. (1999). Detection of 2-hydroxyiminostilbene in the urine of patients taking carbamazepine and its oxidation to a reactive iminoquinone intermediate. J. Pharmacol. Exp. Ther. 288:51-56.
110. Ju, C., and Uetrecht, J.P. (2002). Mechanism of idiosyncratic drug reactions: Reactive metabolite formation, protein binding and the regulation of the immune system. Curr. Drug Metab. 3:367-377.
111. Kalgutkar, A.S., Vaz, A.D.N., Lame, M.E., Henne, K.R., Soglia, J., Zhao, S.X., Abramov, Y.A., Lombardo, F., Collin, C., Hendsch, Z., and Hop, C.E.C.A. (2005). Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P450 3A4. Drug Metab. Dispos. 33:243-253.
112. Kapetanovic, I.M., Torchin, C.D., Strong, J.M., Ynoekawa, W.D., Lu, C., Li, A.P., Dieckhaus, C.M., Santos, W.L., Macdonald, T.L., Sofia, R.D., and Kupferberg, H.J. (2002). Reactivity of atropaldehyde, a felbamate metabolite in human liver tissue in vitro. Chem. Biol. Interact. 142:119-134.
113. 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.
114. Kassahun, K., Pearson, P.G., Tang, W., McIntosh, I., Leung, K., Elmore, C., Dean, D., Wang, R., Doss, G., and Baillie, T.A. (2001). Studies on the metabolism of troglitazone to reactive metabolites in vitro and in vivo. Evidence for novel biotransformation pathways involving quinone methide formation and thiazolidinedione ring scission. Chem. Res. Toxicol. 14:62-70.
115. Kenna, J.G., Satoh, H., Christ, D.D., and Pohl, L.R. (1988). Metabolic basis for a drug hypersensitivity: Antibodies in sera from patients with halothane hepatitis recognize liver neoantigens that contain the trifluoroacetyl group derived from halothane. J. Pharmacol. Exp. Ther. 245:1103-1109.
116. King, C., Tang, W., Ngui, J., Tephly, T., and Braun, M. (2001). Characterization of rat and human UDP-glucuronosyl-transferases responsible for the in vitro glucuronidation of diclofenac. Toxicol. Sci. 61:49-53.
117. Kirkman, S.K., Zhang, M.M.-Y., Horwatt, P.M., and Scatine, J. (1998). Isolation and identification of bromfenac glucoside from rat bile. Drug Metab. Dispos. 26:720-723.
118. Knights, K.M., Cassidy, M.R., and Drew, R. (1986). Benoxaprofen induced toxicity in isolated rat hepatocytes. Toxicology 40:327-339.
119. Knights, K.M., Gasser, R., and Klemisch, W. (2000). In vitro metabolism of acitretin by human liver microsomes: Evidence of an acitretinoyl-coenzyme A thioester conjugate in the transesterification to etretinate. Biochem. Pharmacol. 60:507-516.
120. Koenigs, L.L., Peter, R.M., Hunter, A.P., Haining, R.L., Rettie, A.E., Friedberg, T., Pritchard, M.P., Shor, M., Rushmore, T.H., and Trager, W.F. (1999). Electrospray ionization mass spectrometric analysis of intact cytochrome P450: Identification of tienilic acid adducts to P450 2C9. Biochemistry. 38:2312-2319.
121. Kreiss, C., Amin, S., Nalesnik, M.A., Chopra, K., and Shakil, A.O. (2002). Severe cholestatic hepatitis in a patient taking acitretin. Am. J. Gastroenterol. 97:775-777.
122. Kretz-Rommel, A., and Boelsterli, U.A. (1993). Diclofenac covalent protein binding is dependent on acyl glucuronide formation and is inversely related to P450-mediated acute cell injury in cultured rat hepatocytes. Toxicol. Appl. Pharmacol. 120:155-161.
123. Kretz-Rommel, A., and Boelsterli, U.A. (1994a) Selective protein adducts to membrane proteins in cultured rat hepatocytes exposed to diclofenac: Radiochemical and immunochemical analysis. Mol. Pharmacol. 45:237-244.
124. Kretz-Rommel, A., and Boelsterli, U.A. (1994b). Mechanism of covalent adduct formation of diclofenac to rat hepatic microsomal proteins: Retention of the glucuronic acid moiety in the adduct. Drug Metab. Dispos. 22:956-961.
125. Lake-Bakaar, G., Scheuer, P.J., and Sherlock, S. (1987). Hepatic reactions associated with ketoconazole in the United Kingdom. Br. Med. J. 294:419-422.
126. Lasser, K.E., Allen, P.D., Woolhandler, S.J., Himmelstein, D.U., Wolfe, S.M., and Bor, D.H. (2002). Timing of new black box warnings and withdrawals for prescription medications. JAMA 287:2215-2220.
127. Lazaros, G.A., Stavrinos, C., Papatheodoridis, G.V., Delladetsima, J.K., Toliopoulos, A., and Tasopoulos, N.C. (1996). Amineptine induced liver injury. Report of two cases and brief review of the literature. Hepato-Gastroenterology 43:1015-1019.
128. Lazarou, J., Pomeranz, B.H., and Corey, B.N. (1998). Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA 279:1200-1205.
129. Lecoeur, S., Andre, C., and Beaune, P.H. (1996). Tienilic acid-induced autoimmune hepatitis: Anti-liver and -kidney microsomal type 2 autoantibodies recognize a three-site conformational epitope on cytochrome P4502C9. Mol. Pharmacol. 50:326-333.
130. Lertratanangkoon, K., and Horning, M.G. (1982). Metabolism of carbamazepine. Drug Metab. Dispos. 10:1-10.
131. Letteron, P., Descatoire, V., Tinel, M., Maurel, P., Labbe, G., Loeper, J., Larrey, D., Freneaux, E., and Pessayre, D. (1989). Metabolic activation of the antidepressant tianeptine. I. Cytochrome p-450-mediated in vitro covalent binding. Biochem. Pharmacol. 38:3241-3246.
132. Letteron, P., Fouin-Fortunet, H., Tinel, M., Danan, G., Belghiti, J., and Pessayre, D. (1984). Mechanism for isaxonine hepatitis. I. Metabolic activation by mouse and human cytochrome P-450. J. Pharmacol. Exp. Ther. 229:845-850.
133. Lewis, W., Levine, E.S., Griniuviene, B., Tankersley, K.O., Colacino, J.M., Sommadossi, J.-P., Watanabe, K.A., and Perrino, F.W. (1996). Fialuridine and its metabolites inhibit DNA polymerase γ at sites multiple adjacent analog incorporation, decrease mtDNA abundance, and cause mitochondrial structural defects in cultured hepatoblasts. Proc. Natl. Acad. Sci. USA 93:3592-3597.
134. Li, A.P. (2002). 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. 142:7-23.
135. Li, A.P., Reith, M.K., Rasmussen, A., Gorski, J.C., Hall, S.D., Xu, L., Kaminski, D.L., and Cheng, L.K. (1997). Primary human hepatocytes as a tool for the evaluation of structure-activity relationship in cytochrome P450 induction potential of xenobiotics: Evaluation of rifampin, rifapentine and rifabutin. Chem. Biol. Interact. 107:17-30.
136. Li, X.Q., Bjorkman, A., Andersson, T.B., Ridderstrom, M., and Masimirembwa, C.M. (2002). Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: A new high affinity and turnover enzyme-specific probe substrate. J. Pharmacol. Exp. Ther. 300:399-407.
137. Lind, R.C., Gandolfi, A.J., Sipes, I.G., and Brown, B.R. (1984). The involvement of endotoxin in halothane-associated liver injury. Anesthesiology 61:544-550.
138. Lipsky, J.J., Shen, M.L., and Naylor, S. (2001). Overview - In vitro inhibition of aldehyde dehydrogenase by disulfiram and metabolites. Chem. Biol. Interact. 130-132:81-91.
139. Liu, Z.C., and Uetrecht, J.P. (1995). Clozapine is oxidized by activated human neutrophils to a reactive nitrenium ion that irreversibly binds to the cells. J. Pharmacol. Exp. Ther. 275:1476-1483.
140. Lloyd, S., Hayden, M.J., Sakai, Y., Fackett, A., Silber, P.M., Hewitt, N.J., and Li, A.P. (2002). Differential in vitro hepatotoxicity of troglitazone and rosiglitazone among cryopreserved human hepatocytes from 37 donors. Chem. Biol. Interact. 142:57-71.
141. Lopez-Garcia, M.P., Dansette, P.M., and Mansuy, D. (1994). Thiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: Inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid. Biochemistry 33:166-175.
142. Lopez-Larraza, D.M., Moore, K., Jr., and Dedon, P.C. (2001). Thiols alter the partitioning of calicheamicin-induced deoxyribose 4′-oxidation reactions in the absence of DNA radical repair. Chem. Res. Toxicol. 14:528-535.
143. Lucena, M.I., Andrade, R.J., Rodrigo, L., Salmeron, J., Alvarez, A., Lopez-Garrido, M.J., Camargo, R., and Alcantara, R. (2000). Trovafloxacin- induced acute hepatitis. Clin. Infect. Dis. 30:400-401.
144. Luyendyk, J.P., Maddox, J.F., Cosma, G.N., Ganey, P.E., Cockerell, G.L., and Roth, R.A. (2003). Ranitidine treatment during a modest inflammatory response precipitates idiosyncrasy-like liver injury in rats. J. Pharmacol. Exp. Ther. 307:1227-1234.
145. Macfarlane, B., Davies, S., Mannan, K., Sarsam, R., Pariente, D., and Dooley, J. (1997). Fatal acute fulminant liver failure due to clozapine: A case report and review of clozapine-induced hepatotoxicity. Gastroenterology 112:1707-1709.
146. Madan, A., Parkinson, A., and Faiman, M.D. (1998). Identification of the human P-450 enzymes responsible for the sulfoxidation and thiono-oxidation of diethyldithiocarbamate methyl ester: Role of P-450 enzymes in disulfiram bioactivation. Alcohol Clin. Exp. Res. 22:1212-1219.
147. Madden, S., Woolf, T.F., Pool, W.F., and Park, B.K. (1993). An investigation into the formation of stable, protein-reactive and cytotoxic metabolites from tacrine in vitro. Biochem. Pharmacol. 46:13-20.
148. Madden, S., Spaldin, V., Hayes, R.N., Woolf, T.F., Pool, W.F., and Park, B.K. (1995). Species variation in the bioactivation of tacrine by hepatic microsomes. Xenobiotica 25:103-116.
149. Maggs, J.L., Williams, D., Pirmohamed, M., and Park, B.K. (1995). The metabolic formation of reactive intermediates from clozapine, a drug associated with agranulocytosis in man. J. Pharmacol. Exp. Ther. 275:1463-1475.
150. Mani, C., and Kupfer, D. (1991) Cytochrome P-450-mediated activation and irreversible binding of the antiestrogen tamoxifen to proteins in rat and human liver: Possible involvement of flavin-containing monooxygenases in tamoxifen activation. Cancer Res. 51:6052-6058.
151. Martinat, C., Amar, C., Dansette, P.M., Leclaire, J., Lopez-Garcia, P., Cao, T.D., N'Guyen, H.N., and Mansuy, D. (1992). In vitro metabolism of isaxonine phosphate: Formation of two metabolites, 5-hydroxyisaxonine and 2-aminopyrimidine, and covalent binding to microsomal proteins. Eur. J. Pharmacol. 228:63-71.
152. Masubuchi, Y., and Horie, T. (1999). Mechanism-based inactivation of cytochrome P450s 1A2 and 3A4 by dihydralazine in human liver microsomes. Chem. Res. Toxicol. 12:1028-1032.
153. Masubuchi, Y., Nakano, T., Ose, A., and Horie, T. (2001). Differential selectivity in carbamazepin-induced inactivation of cytochrome p450 enzymes in rat and human liver. Arch. Toxicol. 75:538-543.
154. Matzinger, P. (1994). Tolerance, danger and the extended family. Annu. Rev. Immunol. 12:991-1045.
155. m
156. Mays, D.C., Ortiz-Bermudez, P., Lam, J.P., Tong, I.H., Fauq, A.H., and Lipsky, J.J. (1998). Inhibition of recombinant human mitochondrial aldehyde dehydrogenase by two intermediate metabolites of disulfiram. Biochem. Pharmacol. 55:1099-1103.
157. McKenzie, R., Fried, M.W., Sallie, R., Conjeevaram, H., Di Bisceglie, A.M., Park, Y., Savarese, B., Kleiner, D., Tsokos, M., Luciano, C., Pruett, T., Stotka, J.L., Straus, S.E., and Hoofnagle, J.H. (1995). Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N. Engl. J. Med. 333:1099-1105.
158. Menor, J.A., and Dunham, D.B., Leflunomide. A new agent for the treatment of rheumatoid arthritis. J. Pharm. Soc. Wisc. Sept./Oct. 33-38, 1999.
159. Mitchell, J.E., Morley, J.E., Levine, A.S., Hatsukami, D., Gannon, M., and Pfohl, D. (1987). High-dose naltrexone therapy and dietary counseling for obesity. Biol. Psychiatry 22:35-42.
160. Morgan, M.Y., Reshef, R., Shah, R.R., Oates, N.S., Smith, R.I., and Sherlock, S. (1984). Impaired oxidation of debrisoquine in patients with perhexiline liver injury. Gut 25:1057-1064.
161. Nelson, S.D., Mitchell, J.R., Snodgrass, W.R., and Timbrell, J.A. (1976a). Hepatotoxicity and metabolism of iproniazid and isopropylhydrazine. J. Pharmacol. Exp. Ther. 206:574-585.
162. Nelson, S.D., Mitchell, J.R., Timbrell, J.A., Snodgrass, W.R., and Corcoran, G.B. (1976b). Isoniazid and iproniazid: Activation of metabolites to toxic intermediates in man and rat. Science 193:901-903.
163. Nelson, S.D., Mitchell, J.R., Snodgrass, W.R., and Timbrell, J.A. (1978). Hepatotoxicity and metabolism of iproniazid and isopropylhydrazine. J. Pharmacol. Exp. Ther. 206:574-585.
164. Neuberger, J., Kenna, J.G., Nouri, A.K., and Williams, R. (1985). Antibody mediated hepatocyte injury in methyldopa induced hepatotoxicity. Gut 26:1233-1239.
165. Nissinen, E., Kaheinen, P., Penttila, K.E., Kaivola, J., and Linden, I.-B. (1997). Entacapone, a novel catechol-O-methyl transferase inhibitor for Parkinson's disease, does not impair mitochondrial energy production. Eur. J. Pharmacol. 340:287-294.
166. Njoku, D., Laster, M.J., Gong, D.H., Eger E.I., II, Reed, G.F., and Martin, J.L. (1997). Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: Association between protein acylation and hepatic injury. Anesth. Analg. 84:173-178.
167. Osman, M., Chandrasekaran, A., Chan, K., Scatina, J., Ermer, J., Cevallos, W., and Sisenwine, S.F. (1998). Metabolic disposition of 14C-bromfenac in healthy male volunteers. J. Clin. Pharmacol. 38:744-752.
168. Paliard, P., Vitrey, D., Fournier, G., Belhadjali, J., Patricot, L., and Berger, F. (1978). Perhexiline maleate-induced hepatitis. Digestion 17:419-427.
169. Palmer, W.L., and Woodall, P.S. (1936). Cinchophen - Is there a safe method of administration? J. Amer. Med. Assoc. 107:760-764.
170. Pariente, E.A., Pessayre, D., Bernuau, J., Degott, C., and Benhamou, J.P. (1983). Dihydralazine hepatitis: Report of a case and review of the literature. Digestion 27:47-52.
171. Park, B.K., Pirmohamed, M., and Kitteringham, N.R. (1998). Role of drug disposition in drug hypersensitivity: A chemical, molecular, and clinical perspective. Chem. Res. Toxicol. 11:969-988.
172. Park, B.K., Kitteringham, N.R., Powell, H., and Pirmohamed, M. (2000). Advances in molecular toxicology - Towards understanding idiosyncratic drug toxicity. Toxicology 153:39-60.
173. Paschke, R., Heine, M., Braun, S., and Usadel, K.H. (1993). Mechanisms of hepatotoxicity caused by dacarbazine in rats. J. Cancer Res. Clin. Oncol. 119:475-481.
174. Pellock, J.M. (1999). Pelbamate. Epilepsia 40(Suppl. 5):S57-S62.
175. Pessayre, D., Bichara, M., Feldmann, G., Degott, C., Potet, F. and Benhamou, J.-P. (1979). Perhexiline maleate-induced cirrhosis. Gastroenterology 76, 170-177.
176. Pfohl, D.N., Allen, J.I., Atkinson, R.L., Knopman, D.S., Malcolm, R.J., Mitchell, J.E., and Morley, J.E. (1986). Naltrexone hydrochloride (Trexan): A review of serum transaminase elevations at high dosage. NIDA Res. Monogr. 67:66-72.
177. Pirmohamed, M., Kitteringham, N.R., Guenthner, T.M., Breckenridge, A.M., and Park, B.K. (1992). An investigation of the formation of cytotoxic, protein-reactive and stable metabolites from carbamazepine in vitro. Biochem. Pharmacol. 43:1675-1682.
178. Pirmohamed, M., and Park, B.K. (2001). Genetic susceptibility to adverse drug reactions. Trends Pharmacol. Sci. 22:298-305.
179. Pons, C., Dansette, P.M., Gregeois, J., Homberg, J.C., Billett, E.E., and Mansuy, D. (1996). Human anti-mitochondria autoantibodies appearing in iproniazid-induced immunoallergic hepatitis recognize human liver monoamine oxidase B. Biochem. Biophys. Res. Commun. 218:118-124.
180. Poon, G.K., Chen, Q., Teffera, Y., Ngui, J.S., Griffin, P.R., Braun, M.P., Doss, G.A., Freeden, C., Stearns, R.A., Evans, D.C., Baillie, T.A., and Tang, W. (2001). Bioactivation of diclofenac intermediates- identification of urinary mercapturic acid derivatives in rats and humans. Drug Metab. Dispos. 29:1608-1612.
181. Pottier, J., Busigny, M., and Raynaud, J.P. (1979). Biotransformations of glafenine in the rat and in man. Eur. J. Drug Metab. Pharmacokinet. 4:109-115.
182. Prakash, M., Poreddy, V., Tiyyagura, L., and Bonacini, M. (2001). Jaundice and hepatocellular damage associated with nevirapine therapy. Am. J. Gastroenterol. 96:1571-1574.
183. Pumford, N.R, Myers, T.G., Davila, J.C., Highet, R.J., and Pohl, L.R. (1993). Immunochemical detection of liver protein adducts of the nonsteroidal anti-inflammatory drug diclofenac. Chem. Res. Toxicol. 6:147-150.
184. Pumford, N.J., Halmes, N.C., and Hinson, J.A. (1997). Covalent binding of xenobiotics to specific proteins in the liver. Drug Metab. Rev. 29:39-57.
185. Qui, Y., Burlingame, A.L., and Benet, L.Z. (1998). Mechanisms for covalent binding of benoxaprofen glucuronide to human serum albumin: Studies by tandem mass spectrometry. Drug Metab. Dispos. 26:246-256.
186. Rabkin, J.M., Smith, M.J., Orloff, S.L., Corless, C.L., Stenzel, P., and Olyaei, A.J. (1999). Fatal fulminant hepatitis associated with bromfenac use. Ann. Pharmacother. 33:945-947.
187. Ramachandran, V., Kostrubsky, V.E., Komoroski, B.J., Zhang, S., Dorko, K., Esplen, J.E., Strom, S.C., and Venkataramanan, R. (1999). Troglitazone increases cytochrome P-450 3A protein and activity in primary cultures of human hepatocytes. Drug Metab. Dispos. 27:1194-1199.
188. Reid, J.M., Kuffel, M.J., Miller, J.K., Rios, R., and Ames, M.M. (1999). Metabolic activation of dacarbazine by human cytochromes P450: The role of CYP1A1, CYP1A2, and CYP2E1. Clin. Cancer Res. 5:2192-2197.
189. Riley, R.J., Kitteringham, N.R., and Park, B.K. (1989). Structural requirements for bioactivation of anticonvulsants to cytoxic metabolism in vitro. Br. J. Clin. Pharmacol. 28:482-487.
190. Riska, P., Lamson, M., Macgregor, T., Sabo, J., Hattox, S., Pav, J., and Keirns, J. (1999). Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab. Dispos. 27:895-901.
191. Robin, M.A., Maratrat, M., Le Roy, M., Le Breton, F.P., Bonierbale, E., Dansette, P., Ballet, F., Mansuy, D., and Pessayre, D. (1996). Antigenic targets in tienilic acid hepatitis. Both cytochrome P450 2C11 and 2C11-tienilic acid adducts are transported to the plasma membrane of rat hepatocytes and ecognized by human sera. J. Clin. Invest. 98:1471-1480.
192. Rodman, J.S., Deutsch, D.J., and Gutman, S.I. (1976). Methyldopa hepatitis; A report of six cases and review of the literature. Am. J. Med. 60:941-948.
193. Rodriguez, R.J., and Acosta, D., Jr. (1995). Comparison of ketoconazole- and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology 96:83-92.
194. Rodriguez, R.J., and Acosta, D., Jr. (1997a). N-deacetyl ketoconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology 117:123-131.
195. Rodriguez, R.J., and Acosta, D., Jr. (1997b). Metabolism of ketoconazole and deacetylated ketoconazole by rat hepatic microsomes and flavin-containing monooxygenases. Drug Metab. Dispos. 25:772-777.
196. Roller, S.G., Dieckhaus, D.M., Santos, W.L., Sofia, R.D., and Macdonald, T.L. (2002). Interaction between human serum albumin and the felbamate metabolites 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one and 2-phenylpropenal. Chem. Res. Toxicol. 15:815-824.
197. Rosenblum, L.E., Korn, R.J., and Zimmerman, H.J. (1960). Hepatocellular jaundice as a complication of iproniazid therapy. Arch. Intern. Med. 105:583.
198. Roth, R.A., Luyendyk, J.P., Maddox, J.F., and Ganey, P.E. (2003). Inflammation and drug idiosyncrasy - is there a connection? J. Pharmacol. Exp. Ther. 307:1-8.
199. Roy, S., Francis, F.T., Born, C.K., and Hamrick, M.E. (1980). Interaction of dantrolene with the hepatic mixed function oxidase system. Res. Commun. Chem. Pathol. Pharmacol. 27:507-520.
200. Rozman, E., Galceran, M.T., Anglada, L., and Albet, C. (1995). Investigation of the metabolism of ebrotidine in human urine by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. Drug Metab. Dispos. 23:976-981.
201. Rwagacondo, C.E., Niyitegeka, F., Sarushi, J., Karema, C., Mugisha, V., Dujardin, J.C., Van Overmeir, C., van den Ende, J., and D'Alessandro, U. (2003). Efficacy of amodiaquine alone and combined with sulfadoxine-pyrimethamine and of sulfadoxine pyrimethamine combined with artesunate. Am. J. Trop. Med. Hyg. 68:743-747.
202. Sadeque, A.J.M., Fisher, M.B., Korzekwa, K.R., Gonzalez, F.J., and Rettie, A.E. (1997). Human CYP2C9 and CYP2A6 mediate formation of the hepatotoxin 4-ene-valproic acid. J. Pharmacol. Exp. Ther. 283:698-703.
203. Sahi, J., Hamilton, G., Sinz, M., Barros, S., Huang, S.M., Lesko, L.J., and LeCluyse, E.L. (2000). Effect of troglitazone on cytochrome P450 enzymes in primary cultures of human and rat hepatocytes. Xenobiotica 30:273-284.
204. Satoh, H., Gillette, J.R., Davies, H.W., Schulick, R.D., and Pohl, L.R. (1985). Immunochemical evidence of trifluoroacetylated cytochrome P-450 in the liver of halothane-treated rats. Mol. Pharmacol. 28:468-474,.
205. Satoh, H., Martin, B.M., Schulick, A.H., Christ, D.D., Kenna, J.G., and Pohl, L.R. (1989). Human anti-endoplasmic reticulum antibodies in sera of patients with halothane-induced hepatitis are directed against a trifluoroacetylated carboxylesterase. Proc. Natl. Acad. Sci. USA 86:322-326.
206. Schnyder, B., Mauri-Hellweg, D., Zanni, M., Bettens, F., and Pichler, W.J. (1997). Direct, MHC-dependent presentation of the drug sulfamethoxazole to human alphabeta T cell clones. J. Clin. Invest. 100:136-141.
207. Seitz, S., Kretz-Rommel, A., Oude Elferink, R.P., and Boelsterli, U.A. (1998). Selective protein adduct formation of diclofenac glucuronide is critically dependent on the rat canalicular conjugate export pump (Mrp2). Chem. Res. Toxicol. 11:513-519.
208. Shear, N.H., Spielberg, S.P., Cannon, M., and Miller, M. (1988). Anticonvulsant hypersensitivity syndrome: In vitro risk assessment. J. Clin. Invest. 82:1826-1832.
209. Shen, M.L., Johnson, K.L., Mays, D.C., Lipsky, J.J., and Naylor, S. (2001). Determination of in vivo adducts of disulfiram with mitochondrial aldehyde dehydrogenase. Biochem. Pharmacol. 61:537-545.
210. Shen, S., Hatgus, S.J., Martin, B.M., and Pohl, L.R. (1997). Cytochrome P4502C11 is a target of diclofenac covalent binding in rats. Chem. Res. Toxicol. 10:420-423.
211. Simon, T., Becquemont, L., Mary-Krause, M., deWaziers, I., Beaune, P., Funck-Brentano, C. and Jaillon, P. (2000). Combined glutathione-S-transferase M1 and T1 genetic polymorphism and tacrine hepatotoxicity. Clin. Pharmacol. Ther. 67:432-437.
212. Skibba, J.L., Beal, D.D., Ramirez, G., and Bryan, G.T. (1970). Demethylation of the antineoplastic agent 4(5)-3,3-dimethyl-1-trizeno)- imidazole-5(4)-carboxamide by rats and man. Cancer Res. 30:147-150.
213. Smith, K.S., Smith, P.L., Heady, T.N., Trugman, J.M., Harman, W.D., and Macdonald, T.L. (2003). In vitro metabolism of tolcapone to reactive metabolites: Relevance to tolcapone liver toxicity. Chem. Res. Toxicol. 16:123-128.
214. Spaldin, V., Madden, S., Pool, W.F., and Park, B.K. (1994). The effect of enzyme inhibition on the metabolism and activation of tacrine by human liver microsomes. Br. J. Clin. Pharmacol. 38:15-22.
215. Spearman, M.E., Moloney, S.J., and Prough, R.A. (1984). Effect of cytosolic components on the metabolism of the hydrazide iproniazid. Mol. Pharmacol. 26:566-573.
216. Spracklin, D.K., Hankins, D.C., Fisher, J.M., Thummel, K.E., and Kharasch, E.D. (1997). Cytochrome P450 2E1 is the principal catalyst of human oxidative halothane metabolism in vitro. J. Pharmacol. Exp. Ther. 281:400-411.
217. Stewart, D.E. (2002). Hepatic adverse reactions associated with nefazodone. Can. J. Psychiatry. 47:375-377.
218. Stierlin, H., Faigle, J.W., Sallmann, A., Kung, W., Richter, W.J., Kriemler, H.P., Alt, K.O., and Winkler, T. (1979). Biotransformation of diclofenac sodium (Voltaren) in animals and in man. I. Isolation and identification of principal metabolites. Xenobiotica 9:601-610.
219. Stricker, B.H., Blok, A.P., and Bronkhorst, F.B. (1986). Glafenine-associated hepatic injury. Analysis of 38 cases and review of the literature. Liver 6:63-72.
220. Sutton, T.S., Koblin, D.D., Gruenke, L.D., Weiskopf, R.B., Rampil, I.J., Waskell, L., and Eger, E.I. 2nd. (1991). Fluoride metabolites after prolonged exposure of volunteers and patients to desflurane. Anesth. Analg. 73:180-185.
221. Tang, W., Borel, A.G., Fujimiya, T., and Abbott, F.S. (1995). Fluorinated analogues as mechanistic probes in valproic acid hepatotoxicity: Hepatic microvesicular steatosis and glutathione status. Chem. Res. Toxicol. 8:671-682.
222. Tang, W., Stearns, R.A., Bandiera, S.M., Zhang, Y., Raab, C., Braun, M.P., Dean, D.C., Pang, J., Leung, K.H., Doss, G.A. (1999a). Strauss, J.R., Kwei, G.Y., Rushmore, T.H., Chiu, S.L. and Baillie, T.A., Studies on cytochrome P-450-mediated bioactivation of diclofenac in rats and in human hepatocytes: Identification of glutathione conjugated metabolites. Drug Metab. Dispos. 27:365-372.
223. Tang, W., Stearns, R.A., Wang, R.W., Chiu, S.L., and Baillie, T.A. (1999b). Roles of human hepatic cytochrome P450's 2C9 and 3A4 in the metabolic activation of diclofenac. Chem. Res. Toxicol. 12:192-199.
224. Tettey, J.N., Maggs, J.L., Rapeport, W.G., Pirmohamed, M., and Park, B.K. (2001). Enzyme-induction dependent bioactivation of troglitazone and troglitazone quinone in vivo. Chem. Res. Toxicol. 14:965-974.
225. Thomas, J.A. (2002). Commentary: "Black box" warning labels and drug withdrawals. Toxicol. Appl. Pharmacol. 183:81-82.
226. Thompson, C.D., Kinter, M.T., and Macdonald, T.L. (1996). Synthesis and in vitro reactivity of 3-carbamoyl-2-phenylpropionaldehyde and 2-phenylpropenal: Putative reactive metabolites of felbamate. Chem. Res. Toxicol. 9:1225-1229.
227. Thompson, C.D., Gulden, P.H., and Macdonald, T.L. (1997). Identification of modified atropaldehyde mercapturic acids in rat and human urine after felbamate administration. Chem. Res. Toxicol. 10:457-462.
228. Thompson, D.C., Perera, K., and London, R. (1995). Quinone methide formation from para isomers of methylphenol (cresol), ethylphenol and isopropylphenol: Relationship to toxicity. Chem. Res. Toxicol. 8:55-60.
229. Thompson, D.C., Perera, K., and London, R. (1996). Studies on the mechanism of hepatotoxicity of 4-methylphenol (p-cresol): Effects of deuterium labeling and ring substitution. Chem. Biol. Interact. 101:1-11.
230. Timbrell, J.A., Mitchell, J.R., Snodgrass, W.R., and Nelson, S. (1980). Isoniazid hepatotoxicity: The relationship between covalent binding and metabolism in vivo, J. Pharmacol. Exp. Ther. 213:364-369.
231. Tolman, K.G. (1998). Hepatotoxicity of non-narcotic analgesics. Am. J. Med. 105(1B):13S-19S.
232. Toyoda, Y., Tsuchida, A., Iwami, E., and Miwa, I. (2001). Toxic effect of troglitazone on cultured rat hepatocytes. Life Sci. 68:1867-1876.
233. Tukey, R.H., and Strassburg, C.P. (2000). Human UDP- glucuronosyltransferases: Metabolism, expression and disease. Annu. Rev. Pharmacol. Toxicol. 40:581-616.
234. Uetrecht, J. (1999). New concepts in immunology relevant to idiosyncratic drug reactions: The "danger hypothesis" and innate immune system. Chem. Res. Toxicol. 12:387-395.
235. Uetrecht, J. (2001). Prediction of a new drug's potential to cause idiosyncratic reactions. Curr. Opin. Drug Discov. Develop. 4:55-59.
236. Utili, R., Boitnott, J.K., and Zimmerman, H.J. (1977). Dantrolene-associated hepatic injury. Incidence and character. Gastroenterology 72:610-616.
237. Van Pelt, F.N., and Kenna, J.G. (1994). Formation of trifluoroacetylated protein antigens in cultured rat hepatocytes exposed to halothane in vitro. Biochem. Pharmacol. 48:461-471.
238. Vergani, D., Mieli-Vergani, G., Alberti, A., Neuberger, J., Eddleston, A.L., Davis, M., and Williams, R. (1980). Antibodies to the surface of halothane-altered rabbit hepatocytes in patients with severe halothane-associated hepatitis. N. Engl. J. Med. 303:66-71.
239. Vickers, A.E., Sinclair, J.R., Zollinger, M., Heitz, F., Glanzel, U., Johanson, L., and Fischer, V. (1999). Multiple cytochrome P-450s involved in the metabolism of terbinafine suggest a limited potential for drug-drug interactions. Drug Metab. Dispos. 27:1029-1038.
240. Von Greyerz, S., Zanni, M., Schnyder, B., and Pichler, W.J. (1998). Presentation of non-peptide antigens, in particular drugs, to specific T-cells. Clin. Exp Allergy 28(Suppl. 4):7-11.
241. Von Moltke, L.L. (1999). Nefazodone, meta-chlorophenylpiperazine, and their metabolites in vitro: Cytochromes mediating transformation, and P450-3A4 inhibitory actions. Psychopharmacology (Berl). 145:113-122.
242. Wakabayashi, T., Onda, H., Tada, T., Iijima, M., and Itoh, Y. (1984). High incidence of peliosis hepatitis in autopsy cases of aplastic anemia with special reference to anabolic steroid therapy. Acta Pathol. Jpn. 34:1079-1086.
243. Weber, C., Gasser, R., and Hopfgartner, G. (1999). Absorption, excretion, and metabolism of the endothelin receptor antagonist bosentan in healthy male subjects. Drug Metab. Dispos. 27:810-815.
244. 450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur. J. Clin. Pharmacol. 7:799-804.
245. White, I.N. (2003). Tamoxifen: Is it safe? Comparison of activation and detoxication mechanisms in rodents and in humans. Curr. Drug Metab. 4:223-239.
246. Wolkenstein, P., Tan, C., Lecoeur, S., Wechsler, J., Garcia-Martin, N., Charue, D., Bagot, M., and Beaune, P. (1998). Covalent binding of carbamazepine reactive metabolites to p450 isoforms present in the skin. Chem. Biol. Interact. 113:39-50.
247. Wood, A.J. (1999). The safety of new medicines. JAMA 281:1753-1754.
248. Woolf, T.F., Pool, W.F., Bjorge, S.M., Chang, T., Goel, O.P., Purchase, C.F., Schroeder, M.C., Kunze, K.L., and Trager, W.F. (1993). Bioactivation and irreversible binding of the cognition activator tacrine using human and rat liver microsomal preparations: Species difference. Drug Metab. Dispos. 21:874-882.
249. Wright, G.J., Zeiger, A.V., Leeson, G.A., and Lang, J.F. (1973) The absorption, excretion and metabolism of perhexiline maleate by the human. Postgrad. Med. J. 49:8-15.
250. Wysowski, D.K., and Fourcroy, J.L. (1996). Flutamide hepatotoxicity. J. Urol. 155:209-212.
251. Yamamoto, Y., Yamazaki, H., Ikeda, T., Watanabe, T., Iwabuchi, H., Nakajima, M., and Yokoi, T. (2002). Formation of a novel quinone epoxide metabolite of troglitazone with cytotoxicity to HepG2 cells. Drug Metab. Dispos. 30:155-160.
252. Yamazaki, H., Shibata, A., Suzuki, M., Nakajima, M., Shimada, N., Guengerich, F.P., and Yokoi, T. (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.
253. m aldehyde dehydrogenase. Biochem. Pharmacol. 42:1361-1366.
254. Zanni, M.P., Schnyder, B., von Greyerz, S., and Pichler, W.J. (1998) Involvement of T cells in drug-induced allergies. Trends Pharmacol. Sci. 19:308-310.
255. Zein, N., Sinha, A.M., McGahren, W.J., and Ellestad, G.A. (1988). Calicheamicin gamma II: An antitumor antibiotic that cleaves double stranded DNA site specifically. Science 240:1198-1201.
256. Zein, N., Poncin, M., Nilakantan, R., and Ellestad, G.A. (1989). Calicheamicin gamma II and DNA: Molecular recognition process responsible for site-specificity. Science 244:697-699.
257. Zimmerman, H.J., Hepatotoxicity. The adverse effect of drugs and other chemicals on the liver, 2nd ed. Lippincott, Williams & Wilkins, Philadelphia, 1999.
258. Zimmerman, H.J., Lewis, J.H., Ishak, K.G., and Maddrey, W.C. (1984). Ticrynafen-associated hepatic injury: Analysis of 340 cases. Hepatology 4:315-323.
259. Zimmerman, L.J., Valentine, H.S., Amarnath, K. and Valentine, W.M. (2002). Identification of a S-hexahydro-1H-azepine-1-carbonyl adduct produced by molinate on rat hemoglobin β2 and β3 chains in vivo. Chem. Res. Toxicol. 15:209-217.