NADPH-dependent covalent binding of [3H]paroxetine to human liver microsomes and S-9 fractions: Identification of an electrophilic quinone metabolite of paroxetine

Chemical Research in Toxicology

Volumn 20, Issue 11, 2007, Pages 1649-1657

  Zhao, Sabrina X ^a   Dalvie, Deepak K ^a   Kelly, Joan M ^a   Soglia, John R ^a   Frederick, Kosea S ^a   Smith, Evan B ^a   Obach, R Scott ^a   Kalgutkar, Amit S ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CATECHOL; CYTOCHROME P450 2D6; GLUTATHIONE; PAROXETINE; QUINONE DERIVATIVE; QUINONE METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; S 9; SCAVENGER; UNCLASSIFIED DRUG;

ARTICLE; COVALENT BOND; DRUG ACTIVITY; ELECTRON; ELECTROPHILIC STRESS; ENZYME INACTIVATION; ENZYME METABOLISM; INCUBATION TIME; LIQUID CHROMATOGRAPHY; LIVER MICROSOME; MASS SPECTROMETRY; MICHAEL ADDITION; OXIDATION;

BIOTRANSFORMATION; CYTOCHROME P-450 CYP2D6; GLUTATHIONE; HUMANS; MICROSOMES, LIVER; NADP; PAROXETINE; QUINONES; TRITIUM;

EID: 37249018714     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx700132x     Document Type: Article

References (35)

1. Baillie, T. A. (2006) Future of toxicology - Metabolic activation and dreg design: Challenges and opportunities in chemical toxicology. Chem. Res. Toxicol. 19, 889-893.
2. 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 dreg discovery and development. Chem. Res. Toxicol. 17, 3-16.
3. Kalgutkar, A. S., and Soglia, J. R. (2005) Minimising the potential for metabolic activation in dreg discovery. Exp. Opin. Drug Metab. Toxicol. 1, 91-142.
4. Kalgutkar, A. S., Gardner, I., Obach, R. S., Shaffer, C. L., Callegari, E., Henne, K. R., Mutlib, A. E., Dalvie, D. K., Lee, J. S., Nakai, Y., O'Donnell, J. P., Boer, J., and Harriman, S. P. (2005) A comprehensive listing of bioactivation pathways of organic functional groups. Curr. Drug Metab. 6, 161-225.
5. Colakoglu, O., Tankurt, E., Unsal, B., Ugur, F., Kuperlioglu, A., Buyrac, Z., and Akpinar, Z. (2005) Toxic hepatitis associated with paroxetine. Int. J. Clin. Pract. 59, 861-862.
6. Azaz-Livshits, T., Hershko, A., and Ben-Chetrit, E. (2002) Paroxetine associated hepatotoxicity: A report of 3 cases and a review of the literature. Pharmacopsychiatry 35, 112-115.
7. Benbow, S. J., and Gill, G. (1997) Paroxetine and hepatotoxicity. Br. Med. J. 314, 1387.
8. 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.
9. Haddock, R. E., Johnson, A. M., Langley, P. F., Nelson, D. R., Pope, J. A., Thomas, D. R., and Woods, F. R. (1989) Metabolic pathways of paroxetine in animals and man and the comparative pharmacological properties of the its metabolites. Acta Psychiatr. Scand. Suppl. 350, 24-26.
10. Murray, M. (2000) Mechanisms of inhibitory and regulatory effects of methylenedioxyphenyl compounds on cytochrome P450-dependent drug oxidation. Curr. Drug Metab. 1, 67-84.
11. Bertelsen, K. M., Venkatakrishnan, K., Von Moltke, L. L., Obach, R. S., and Greenblatt, D. J. (2003) Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: Comparison with fluoxetine and quinidine. Drug Metab. Dispos. 31, 289-293.
12. Brøsen, K., Hansen, J. G., Nielsen, K. K., Sindrup, S. H., and Gram, L. F. (1993) Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. Eur. J. Clin. Pharmacol. 44, 349-355.
13. Alderman, J., Preskorn, S. H., Greenblatt, D. J., Harrison, W., Penenberg, D., Allison, J., and Chung, M. (1997) Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers. J. Clin. Phychopharmacol. 17, 284-291.
14. Hemeryck, A., Lefebvre, R. A., De Vriendt, C., and Belpaire, F. M. (2000) Paroxetine affects metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers. Clin. Pharmacol. Ther. 67, 283-291.
15. Spina, E., Avenoso, A., Facciola, G., Scordo, M. G., Ancione, M., and Madia, A. (2001) Plasma concentrations of risperidone and 9-hydroxyrisperidone during combined treatment with paroxetine. Ther. Drug Monit. 23, 223-227.
16. Belle, D. J., Ernest, C. S., Sauer, J. M., Smith, B. P., Thomasson, H. R., and Witcher, J. W. (2002) Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. J. Clin. Pharmacol. 42, 1219-1227.
17. Venkatakrishnan, K., and Obach, R. S. (2005) In vitro-in vivo extrapolation of CYP2D6 inactivation by paroxetine: Prediction of nonstationary pharmacokinetics and drug interaction magnitude. Drug Metab. Dispos. 33, 845-852.
18. Obach, R. S., Walsky, R. L., and Venkatakrishnan, K. (2007) Mechanism-based inactivation of human cytochrome P450 enzymes and the prediction of drug-drug interactions. Drug Metab. Dispos. 35, 246-255.
19. Baillie, T. A., and Davis, M. R. (1993) Mass spectrometry in the analysis of glutathione conjugates. Biol. Mass Spectrom. 22, 319-325.
20. Napolitano, A., Memoli, S., and Prota, G. (1999) A new insight in the biosynthesis of pheomelanins: characterization of a labile 1,4-benzothiazine intermediate. J. Org. Chem. 64, 3009-3011.
21. Sindrup, S. H., Brøsen, K., and Gram, L. F. (1992) Pharmacokinetics of the selective serotonin reuptake inhibitor paroxetine: Nonlinearity and relation to the sparteine oxidation polymorphism. Clin. Pharmacol. Ther. 51, 288-295.
22. Bloomer, J. C., Woods, F. R., Haddock, R. E., Lennard, M. S., and Tucker, G. T. (1992) The role of cytochrome P4502D6 in the metabolism of paroxetine by human liver microsomes. Br. J. Clin. Pharmacol. 33, 521-523.
23. Fukuto, J. M., Kumagai, Y., and Cho, A. K. (1991) Determination of the mechanism of demethylenation of (methylenedioxy)phenyl compounds by cytochrome P450 using deuterium isotope effects. J. Med. Chem. 34, 2871-2876.
24. Monks, T. J., and Jones, D. C. (2002) The metabolism and toxicity of quinones, quinonimines, quinone methides, and quinone-thioethers. Curr. Drug Metab. 3, 425-438.
25. Bolton, J. L., Trush, M. A., Penning, T. M., Dryhurst, G., and Monks, T. J. (2000) Roles of quinones in toxicity. Chem. Res. Toxicol. 13, 135-160.
26. Monks, T. J., Hanzlik, R. P., Cohen, G. M., Ross, D., and Graham, D. G. (1992) Quinone chemistry and toxicity. Toxicol. Appl. Pharmacol. 112, 2-16.
27. Bolton, J. L. (2002) Quinoids, quinoid radicals, and phenoxyl radicals formed from estrogens and antiestrogens. Toxicology 177, 55-65.
28. Butterworth, M., Lau, S. S., and Monks, T. J. (1996) 17 beta-Estradiol metabolism by hamster hepatic microsomes. Implications for the catechol-O-methyl transferase-mediated detoxication of catechol estrogens. Drug Metab. Dispos. 24, 588-594.
29. Taskinen, J., Ethell, B. T., Pihlavisto, P., Hood, A. M., Burchell, B., and Coughtrie, M. W. (2003) Conjugation of catechols by recombinant human sulfotransferases, UDP-glucuronosyltransferases, and soluble catechol O-methyltransferase: Structure-conjugation relationships and predictive models. Drug Metab. Dispos. 31, 1187-1197.
30. 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.
31. Samuel, K., Yin, W., Steams, R. A., Tang, Y. S., Chaudhary, A. G., Jewell, J. P., Lanza, T., Lin, L. S., Hagmann, W. K., Evans, D. C., and Kumar, S. (2003) Addressing the metabolic activation potential of new leads in drug discovery: A case study using ion trap mass spectrometry and tritium labeling techniques. J. Mass Spectrom. 38, 211-221.
32. Wong, K. S., Goyal, R. N., Wrona, M. Z., Blank, C. L., and Dryhurst, G. (1993) 7-S-glutathionyl-tryptamine-4,5-dione: A possible aberrant metabolite of serotonin. Biochem. Pharmacol. 46, 1637-1652.
33. Erve, J. C., Svensson, M. A., von Euler-Chelpin, H., and Klasson-Wehler, E. (2004) Characterization of glutathione conjugates of the remoxipride hydroquinone metabolite NCQ-344 formed in vitro and detection following oxidation by human neutrophils. Chem. Res. Toxicol. 17, 564-571.
34. Miller, R. T., Lau, S. S., and Monks, T. J. (1997) 2,5-Bis-(glutathion-S- yl)-alpha-methyldopamine, a putative metabolite of (+/-)-3,4- methylenedioxyamphetamine, decreases brain serotonin concentrations. Eur. J. Pharmacol. 323, 173-180.
35. Ozdemir, V., Tyndale, R. F., Reed, K., Herrmann, N., Sellers, E. M., Kalow, W., and Naranjo, C. A. (1999) Paroxetine steady-state plasma concentration in relation to CYP2D6 genotype in extensive metabolizers. J. Clin. Psychopharmacol. 19, 472-475.