In vitro screening of 50 highly prescribed drugs for thiol adduct formation - Comparison of potential for drug-induced toxicity and extent of adduct formation

Chemical Research in Toxicology

Volumn 22, Issue 4, 2009, Pages 690-698

  Gan, Jinping ^a   Ruan, Qian ^a   He, Bing ^a   Zhu, Mingshe ^a   Shyu, Wen C ^a   Humphreys, W Griffith ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBAMAZEPINE; CLOZAPINE; DANSYL CHLORIDE; DANSYL GLUTATHIONE; DICLOFENAC; DULOXETINE; FLUTAMIDE; LANSOPRAZOLE; LOSARTAN; MONTELUKAST; NIMESULIDE; OMEPRAZOLE; PARACETAMOL; PAROXETINE; PHENYTOIN; PULEGONE; RALOXIFENE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; RISPERIDONE; ROSIGLITAZONE; SIMVASTATIN; TERBINAFINE; THIOL DERIVATIVE; TROGLITAZONE; UNCLASSIFIED DRUG; ZILEUTON;

ARTICLE; CONTROLLED STUDY; DRUG SCREENING; DRUG STRUCTURE; FLUORESCENCE; HUMAN; HUMAN CELL; IN VITRO STUDY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLITE; OXIDATION; QUANTITATIVE ANALYSIS;

CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DANSYL COMPOUNDS; GLUTATHIONE; HUMANS; LIVER; MASS SPECTROMETRY; PRESCRIPTION DRUGS;

EID: 66149104042     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx800368n     Document Type: Article

References (56)

1. Baillie, T. A. (2006) Future of toxicology-metabolic activation and drug design: Challenges and opportunities in chemical toxicology. Chem. Res. Toxicol. 19, 889-893. (Pubitemid 44092354)
2. Guengerich, F. P., and MacDonald, J. S. (2007) Applying mechanisms of chemical toxicity to predict drug safety. Chem. Res. Toxicol. 20, 344-369. (Pubitemid 46548682)
3. Park, B. K., Kitteringham, N. R., Maggs, J. L., Pirmohamed, M., and Williams, D. P. (2005) The role of metabolic activation in drug-induced hepatotoxicity. Annu. Rev. Pharmacol. Toxicol. 45, 177-202. (Pubitemid 40261802)
4. Uetrecht, J. (2008) Idiosyncratic drug reactions: Past, present, and future. Chem. Res. Toxicol. 21, 84-92.
5. Walgren, J. L., Mitchell, M. D., and Thompson, D. C. (2005) Role of metabolism in drug-induced idiosyncratic hepatotoxicity. Crit. Rev. Toxicol. 35, 325-361. (Pubitemid 40691298)
6. Kumar, S., Kassahun, K., Tschirret-Guth, R. A., Mitra, K., and Baillie, T. A. (2008) Minimizing metabolic activation during pharmaceutical lead optimization: Progress, knowledge gaps and future directions. Curr. Opin. Drug Discovery Dev. 11, 43-52.
7. Kamel, A., and Prakash, C. (2006) High performance liquid chromatography/atmospheric pressure ionization/tandem mass spectrometry (HPLC/API/MS/MS) in drug metabolism and toxicology. Curr. Drug Metab. 7, 837-852.
8. Chen, Y., Monshouwer, M., and Fitch, W. L. (2007) Analytical tools and approaches for metabolite identification in early drug discovery. Pharm. Res. 24, 248-257. (Pubitemid 46072184)
9. Ma, S., and Subramanian, R. (2006) Detecting and characterizing reactive metabolites by liquid chromatography/tandem mass spectrometry. J. Mass Spectrom. 41, 1121-1139. (Pubitemid 44454166)
10. Physician's Desk Reference (PDR), published online by Thomson Reuters, Montvale, NJ, http://www.pdr.net.
11. Gan, J., Harper, T. W., Hsueh, M. M., Qu, Q., and Humphreys, W. G. (2005) Dansyl glutathione as a trapping agent for the quantitative estimation and identification of reactive metabolites. Chem. Res. Toxicol. 18, 896-903. (Pubitemid 40705457)
12. Zheng, J., Ma, L., Xin, B., Olah, T., Humphreys, W. G., and Zhu, M. (2007) Screening and identification of GSH-trapped reactive metabolites using hybrid triple quadruple linear ion trap mass spectrometry. Chem. Res. Toxicol. 20, 757-766. (Pubitemid 46953682)
13. Nelson, S. D., McClanahan, R. H., Thomassen, D., Gordon, W. P., and Knebel, N. (1992) Investigations of mechanisms of reactive metabolite formation from (R)-(+)-pulegone. Xenobiotica 22, 1157-1164.
14. 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. (Pubitemid 38134055)
15. Weidolf, L., Karlsson, K. E., and Nilsson, I. (1992) A metabolic route of omeprazole involving conjugation with glutathione identified in the rat. Drug Metab. Dispos. 20, 262-267.
16. Sachs, G., Shin, J. M., Briving, C., Wallmark, B., and Hersey, S. (1995) The pharmacology of the gastric acid pump: The H+, K+ ATPase. Annu. Rev. Pharmacol. Toxicol. 35, 277-305.
17. Nicoll-Griffith, D. A., Gupta, N., Twa, S. P., Williams, H., Trimble, L. A., and Yergey, J. A. (1995) Verlukast (MK-0679) conjugation with glutathione by rat liver and kidney cytosols and excretion in the bile. Drug Metab. Dispos. 23, 1085-1093.
18. Chen, Q., Ngui, J. S., Doss, G. A., Wang, R. W., Cai, X., DiNinno, F. P., Blizzard, T. A., Hammond, M. L., Stearns, R. A., Evans, D. C., Baillie, T. A., and Tang, W. (2002) Cytochrome P450 3A4-mediated bioactivation of raloxifene: Irreversible enzyme inhibition and thiol adduct formation. Chem. Res. Toxicol. 15, 907-914.
19. Alvarez-Sanchez, R., Montavon, F., Hartung, T., and Pahler, A. (2006) Thiazolidinedione bioactivation: A comparison of the bioactivation potentials of troglitazone, rosiglitazone, and pioglitazone using stable isotope-labeled analogues and liquid chromatography tandem mass spectrometry. Chem. Res. Toxicol. 19, 1106-1116. (Pubitemid 44384842)
20. Yan, Z., Li, J., Huebert, N., Caldwell, G. W., Du, Y., and Zhong, H. (2005) Detection of a novel reactive metabolite of diclofenac: Evidence for CYP2C9-mediated bioactivation via arene oxides. Drug Metab. Dispos. 33, 706-713. (Pubitemid 40686621)
21. Yu, L. J., Chen, Y., Deninno, M. P., O'Connell, T. N., and Hop, C. E. (2005) Identification of a novel glutathione adduct of diclofenac, 4′-hydroxy-2′-glutathion-deschloro-diclofenac, upon incubation with human liver microsomes. Drug Metab. Dispos. 33, 484-488. (Pubitemid 40393189)
22. Tang, W. (2003) The metabolism of diclofenac - Enzymology and toxicology perspectives. Curr. Drug Metab. 4, 319-329. (Pubitemid 36958332)
23. 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. (Pubitemid 3017337)
24. Gardner, I., Zahid, N., MacCrimmon, D., and Uetrecht, J. P. (1998) A comparison of the oxidation of clozapine and olanzapine to reactive metabolites and the toxicity of these metabolites to human leukocytes. Mol. Pharmacol. 53, 991-998. (Pubitemid 28280440)
25. 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. (Pubitemid 32800152)
26. 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 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. (Pubitemid 32064376)
27. He, K., Talaat, R. E., Pool, W. F., Reily, M. D., Reed, J. E., Bridges, A. J., and Woolf, T. F. (2004) Metabolic activation of troglitazone: Identification of a reactive metabolite and mechanisms involved. Drug Metab. Dispos. 32, 639-646. (Pubitemid 38668157)
28. Chen, W., Koenigs, L. L., Thompson, S. J., Peter, R. M., Rettie, A. E., Trager, W. F., and Nelson, S. D. (1998) Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6. Chem. Res. Toxicol. 11, 295-301. (Pubitemid 28194352)
29. Zhao, S. X., Dalvie, D. K., Kelly, J. M., Soglia, J. R., Frederick, K. S., Smith, E. B., Obach, R. S., and Kalgutkar, A. S. (2007) NADPH-dependent covalent binding of [3H]paroxetine to human liver microsomes and S-9 fractions: Identification of an electrophilic quinone metabolite of paroxetine. Chem. Res. Toxicol. 20, 1649-1657. (Pubitemid 350275610)
30. Soglia, J. R., Contillo, L. G., Kalgutkar, A. S., Zhao, S., Hop, C. E., Boyd, J. G., and Cole, M. J. (2006) A semiquantitative method for the determination of reactive metabolite conjugate levels in vitro utilizing liquid chromatography-tandem mass spectrometry and novel quaternary ammonium glutathione analogues. Chem. Res. Toxicol. 19, 480-490.
31. 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. (Pubitemid 32173319)
32. 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.
33. Joshi, E. M., Heasley, B. H., Chordia, M. D., and Macdonald, T. L. (2004) In vitro metabolism of 2-acetylbenzothiophene: Relevance to zileuton hepatotoxicity. Chem. Res. Toxicol. 17, 137-143. (Pubitemid 38252492)
34. 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. (Pubitemid 35232556)
35. Munns, A. J., De Voss, J. J., Hooper, W. D., Dickinson, R. G., and Gillam, E. M. (1997) Bioactivation of phenytoin by human cytochrome P450: Characterization of the mechanism and targets of covalent adduct formation. Chem. Res. Toxicol. 10, 1049-1058. (Pubitemid 27418023)
36. Pearce, R. E., Lu, W., Wang, Y., Uetrecht, J. P., Correia, M. A., and Leeder, J. S. (2008) Pathways of carbamazepine bioactivation in vitro. III. The role of human cytochrome P450 enzymes in the formation of 2,3- dihydroxycarbamazepine. Drug Metab. Dispos. 36, 1637-1649.
37. Pearce, R. E., Uetrecht, J. P., and Leeder, J. S. (2005) Pathways of carbamazepine bioactivation in vitro: II. The role of human cytochrome P450 enzymes in the formation of 2-hydroxyiminostilbene. Drug Metab. Dispos. 33, 1819-1826. (Pubitemid 41697267)
38. Obach, R. S., Kalgutkar, A. S., Soglia, J. R., and Zhao, S. X. (2008) Can in vitro metabolism-dependent covalent binding data in liver microsomes distinguish hepatotoxic from nonhepatotoxic drugs? An analysis of 18 drugs with consideration of intrinsic clearance and daily dose. Chem. Res. Toxicol. 21, 1814-1822.
39. Mitchell, J. R., Snodgrass, W. R., and Gillette, J. R. (1976) The role of biotransformation in chemical-induced liver injury. Environ. Health Perspect. 15, 27-38. (Pubitemid 8005197)
40. Khojasteh-Bakht, S. C., Chen, W., Koenigs, L. L., Peter, R. M., and Nelson, S. D. (1999) Metabolism of (R)-(+)-pulegone and (R)-(+)-menthofuran by human liver cytochrome P-450s: Evidence for formation of a furan epoxide. Drug Metab. Dispos. 27, 574-580. (Pubitemid 29214468)
41. Mannens, G., Huang, M. L., Meuldermans, W., Hendrickx, J., Woestenborghs, R., and Heykants, J. (1993) Absorption, metabolism, and excretion of risperidone in humans. Drug Metab. Dispos. 21, 1134-1141. (Pubitemid 23348354)
42. Lantz, R. J., Gillespie, T. A., Rash, T. J., Kuo, F., Skinner, M., Kuan, H. Y., and Knadler, M. P. (2003) Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects. Drug Metab. Dispos. 31, 1142-1150. (Pubitemid 37048286)
43. Merck & Co., Inc. (2008) Zocor (Simvastatin) Tablets, U.S. Prescribing Information, http://www.merck.com/product/usa/pi-circulars/z/zocor/ zocor-pi.pdf.
44. Neuvonen, P. J., Kantola, T., and Kivisto, K. T. (1998) Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin. Pharmacol. Ther. 63, 332-341. (Pubitemid 28182231)
45. Cox, P. J., Ryan, D. A., Hollis, F. J., Harris, A.-M., Miller, A. K., Vousden, M., and Cowley, H. (2000) Absorption, disposition, and metabolism of rosiglitazone, a potent thiazolidinedione insulin sensitizer, in humans. Drug Metab. Dispos. 28, 772-780. (Pubitemid 30470827)
46. van Harten, J. (1993) Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clin. Pharmacokinet. 24, 203-220. (Pubitemid 23094387)
47. Kaye, C. M., Haddock, R. E., Langley, P. F., Mellows, G., Tasker, T. C., Zussman, B. D., and Greb, W. H. (1989) A review of the metabolism and pharmacokinetics of paroxetine in man. Acta Psychiatr. Scand. Suppl. 350, 60-75. (Pubitemid 19236643)
48. Sica, D. A., Gehr, T. W., and Ghosh, S. (2005) Clinical pharmacokinetics of losartan. Clin. Pharmacokinet. 44, 797-814. (Pubitemid 41126929)
49. Eli Lilly and Company (2007) EVISTA (Raloxifene Hydrochloride) Tablet for Oral Use, U.S. Prescribing Information, http://pi.lilly.com/us/evista-pi.pdf.
50. Forrest, J. A., Clements, J. A., and Prescott, L. F. (1982) Clinical pharmacokinetics of paracetamol. Clin. Pharmacokinet. 7, 93-107. (Pubitemid 12070476)
51. Siegers, C. P., Loeser, W., Gieselmann, J., and Oltmanns, D. (1984) Biliary and renal excretion of paracetamol in man. Pharmacology 29, 301-303. (Pubitemid 14048914)
52. Davies, N. M., and Anderson, K. E. (1997) Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls. Clin. Pharmacokinet. 33, 184-213. (Pubitemid 27399546)
53. 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. (Pubitemid 10167099)
54. Novartis Pharmaceuticals Corporation (2008) CLOZARIL (Clozapine) Tablets, U.S. Precribing Information, http://www.pharma.us.novartis.com/product/pi/pdf/ Clozaril.pdf.
55. Loi, C. M., Young, M., Randinitis, E., Vassos, A., and Koup, J. R. (1999) Clinical pharmacokinetics of troglitazone. Clin. Pharmacokinet. 37, 91-104. (Pubitemid 29431478)
56. Bernareggi, A. (1998) Clinical pharmacokinetics of nimesulide. Clin. Pharmacokinet. 35, 247-274. (Pubitemid 28491213)