Characterization of human cytochrome P450s involved in the bioactivation of clozapines

Drug Metabolism and Disposition

Volumn 41, Issue 3, 2013, Pages 651-658

  Dragovic, Sanja ^a   Gunness, Patrina ^b   Ingelman Sundberg, Magnus ^b   Vermeulen, Nico P E ^a   Commandeur, Jan N M ^a  

^a VU UNIVERSITY AMSTERDAM   (Netherlands)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CLOZAPINE; CLOZAPINE N OXIDE; CYTOCHROME P450; CYTOCHROME P450 3A4; CYTOCHROME P450 3D6; DRUG METABOLITE; GLUTATHIONE; NORCLOZAPINE; QUINIDINE; RECOMBINANT ENZYME; UNCLASSIFIED DRUG;

AEROBIC METABOLISM; ARTICLE; CONTROLLED STUDY; DEMETHYLATION; DRUG CLEARANCE; DRUG METABOLISM; DRUG OXIDATION; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME KINETICS; HUMAN; LIVER MICROSOME; PRIORITY JOURNAL;

ANTIPSYCHOTIC AGENTS; BIOTRANSFORMATION; CLOZAPINE; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME SYSTEM; DEALKYLATION; ENZYME INHIBITORS; GLUTATHIONE; HUMANS; ISOENZYMES; KINETICS; LIVER; MICROSOMES, LIVER; MOLECULAR STRUCTURE; OXIDATION-REDUCTION; RECOMBINANT PROTEINS;

EID: 84874041641     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.112.050484     Document Type: Article

References (46)

1. Argoti D, Liang L, Conteh A, Chen L, Bershas D, Yu CP, Vouros P, and Yang E (2005) Cyanide trapping of iminium ion reactive intermediates followed by detection and structure identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chem Res Toxicol 18:1537-1544.
2. Arranz MJ, Dawson E, Shaikh S, Sham P, Sharma T, Aitchison K, Crocq MA, Gill M, Kerwin R, and Collier DA (1995) Cytochrome P4502D6 genotype does not determine response to clozapine. Br J Clin Pharmacol 39:417-420.
3. Baldwin SJ, Bloomer JC, Smith GJ, Ayrton AD, Clarke SE, and Chenery RJ (1995) Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9. Xenobiotica 25: 261-270.
4. Barbara JE and Castro-Perez JM (2011) High-resolution chromatography/time-of-flight MSE with in silico data mining is an information-rich approach to reactive metabolite screening. Rapid Commun Mass Spectrom 25:3029-3040.
5. Bertilsson L, Carrillo JA, Dahl ML, Llerena A, Alm C, Bondesson U, Lindström L, Rodriguez de la Rubia I, Ramos S, and Benitez J (1994) Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. Br J Clin Pharmacol 38:471-473.
6. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248-254.
7. Buchanan RW (1995) Clozapine: efficacy and safety. Schizophr Bull 21:579-591.
8. Centorrino F, Baldessarini RJ, Kando JC, Frankenburg FR, Volpicelli SA, and Flood JG (1994) Clozapine and metabolites: concentrations in serum and clinical findings during treatment of chronically psychotic patients. J Clin Psychopharmacol 14:119-125.
9. Cohen LG, Chesley S, Eugenio L, Flood JG, Fisch J, and Goff DC (1996) Erythromycin-induced clozapine toxic reaction. Arch Intern Med 156:675-677.
10. Dahl ML, Llerena A, Bondesson U, Lindström L, and Bertilsson L (1994) Disposition of clozapine in man: lack of association with debrisoquine and S-mephenytoin hydroxylation polymorphisms. Br J Clin Pharmacol 37:71-74.
11. Dai D, Tang J, Rose R, Hodgson E, Bienstock RJ, Mohrenweiser HW, and Goldstein JA (2001) Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther 299:825-831.
12. Dain JG, Nicoletti J, and Ballard F (1997) Biotransformation of clozapine in humans. Drug Metab Dispos 25:603-609.
13. Damsten MCA, van Vugt-Lussenburg BMA, Zeldenthuis T, de Vlieger JS, Commandeur JNM, and Vermeulen NPE (2008) Application of drug metabolising mutants of cytochrome P450 BM3 (CYP102A1) as biocatalysts for the generation of reactive metabolites. Chem Biol Interact 171:96-107.
14. Dragovic S, Boerma JS, van Bergen L, Vermeulen NPE, and Commandeur JNM (2010) Role of human glutathione S-transferases in the inactivation of reactive metabolites of clozapine. Chem Res Toxicol 23:1467-1476.
15. Eiermann B, Engel G, Johansson I, Zanger UM, and Bertilsson L (1997) The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol 44:439-446.
16. Eiselt R, Domanski TL, Zibat A, Mueller R, Presecan-Siedel E, Hustert E, Zanger UM, Brockmoller J, Klenk HP, and Meyer UA, et al. (2001) Identification and functional characterization of eight CYP3A4 protein variants. Pharmacogenetics 11:447-458.
17. Fang J, Coutts RT, McKenna KF, and Baker GB (1998) Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine. Naunyn Schmiedebergs Arch Pharmacol 358:592-599.
18. Fischer V, Haar JA, Greiner L, Lloyd RV, and Mason RP (1991) Possible role of free radical formation in clozapine (clozaril)-induced agranulocytosis. Mol Pharmacol 40:846-853.
19. Fischer V, Vogels B, Maurer G, and Tynes RE (1992) The antipsychotic clozapine is metabolized by the polymorphic human microsomal and recombinant cytochrome P450 2D6. J Pharmacol Exp Ther 260:1355-1360.
20. Habig WH, Pabst MJ, and Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130-7139.
21. Hiratsuka M (2012) In vitro assessment of the allelic variants of cytochrome P450. Drug Metab Pharmacokinet 27:68-84.
22. Hosomi H, Fukami T, Iwamura A, Nakajima M, and Yokoi T (2011) Development of a highly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation. Drug Metab Dispos 39:1388-1395.
23. Hummer M, Kurz M, Kurzthaler I, Oberbauer H, Miller C, and Fleischhacker WW (1997) Hepatotoxicity of clozapine. J Clin Psychopharmacol 17:314-317.
24. Jerling M, Lindström L, Bondesson U, and Bertilsson L (1994) Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit 16:368-374.
25. Khojasteh SC, Prabhu S, Kenny JR, Halladay JS, and Lu AY (2011) Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity. Eur J Drug Metab Pharmacokinet 36:1-16.
26. Li F, Lu J, and Ma X (2011) Profiling the reactive metabolites of xenobiotics using metabolomic technologies. Chem Res Toxicol 24:744-751.
27. Lin T, Pan K, Mordenti J, and Pan L (2007) In vitro assessment of cytochrome P450 inhibition: strategies for increasing LC/MS-based assay throughput using a one-point IC(50) method and multiplexing high-performance liquid chromatography. J Pharm Sci 96:2485-2493.
28. Linnet K and Olesen OV (1997) Metabolism of clozapine by cDNA-expressed human cytochrome P450 enzymes. Drug Metab Dispos 25:1379-1382.
29. Liu ZC and Uetrecht JP (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.
30. Maggs JL, Williams D, Pirmohamed M, and Park BK (1995) The metabolic formation of reactive intermediates from clozapine, a drug associated with agranulocytosis in man. J Pharmacol Exp Ther 275:1463-1475.
31. Newton DJ, Wang RW, and Lu AY (1995) Cytochrome P450 inhibitors. Evaluation of specificities in the in vitrometabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 23:154-158.
32. Olesen OV and Linnet K (2001) Contributions of five human cytochrome P450 isoforms to the Ndemethylation of clozapine in vitro at low and high concentrations. J Clin Pharmacol 41: 823-832.
33. Ono S, Hatanaka T, Hotta H, Satoh T, Gonzalez FJ, and Tsutsui M (1996) Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNAexpressed human P450s and human liver microsomes. Xenobiotica 26:681-693.
34. Pirmohamed M, Williams D, Madden S, Templeton E, and Park BK (1995) Metabolism and bioactivation of clozapine by human liver in vitro. J Pharmacol Exp Ther 272:984-990.
35. Rea V, Dragovic S, Boerma JS, de Kanter FJ, Vermeulen NPE, and Commandeur JNM (2011) Role of residue 87 in the activity and regioselectivity of clozapine metabolism by drugmetabolizing CYP102A1 M11H: application for structural characterization of clozapine GSH conjugates. Drug Metab Dispos 39:2411-2420.
36. Rousu T, Pelkonen O, and Tolonen A (2009) Rapid detection and characterization of reactive drug metabolites in vitro using several isotope-labeled trapping agents and ultra-performance liquid chromatography/time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 23: 843-855.
37. Safferman A, Lieberman JA, Kane JM, Szymanski S, and Kinon B (1991) Update on the clinical efficacy and side effects of clozapine. Schizophr Bull 17:247-261.
38. Schaber G, Wiatr G, Wachsmuth H, Dachtler M, Albert K, Gaertner I, and Breyer-Pfaff U (2001) Isolation and identification of clozapine metabolites in patient urine. Drug Metab Dispos 29: 923-931.
39. Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423.
40. Slavik R, Peters JU, Giger R, Bürkler M, and Bald E (2011) Synthesis of potential drug metabolites by a modified Udenfriend reaction. Tetrahedron Lett 52:749-752 DOI: 10.1016/ j.tetlet.2010.12.014.
41. Thompson RA, Isin EM, Li Y, Weidolf L, Page K, Wilson I, Swallow S, Middleton B, Stahl S, and Foster AJ, et al. (2012) In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs. Chem Res Toxicol 25:1616-1632.
42. Tugnait M, Hawes EM, McKay G, Eichelbaum M, and Midha KK (1999) Characterization of the human hepatic cytochromes P450 involved in the in vitro oxidation of clozapine. Chem Biol Interact 118:171-189.
43. Wagstaff AJ and Perry CM (2003) Clozapine: in prevention of suicide in patients with schizophrenia or schizoaffective disorder. CNS Drugs 17:273-280, discussion 281-283.
44. Wen B, Ma L, Nelson SD, and Zhu M (2008) High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry. Anal Chem 80:1788-1799.
45. Westlind A, Löfberg L, Tindberg N, Andersson TB, and Ingelman-Sundberg M (1999) Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 59-upstream regulatory region. Biochem Biophys Res Commun 259:201-205.
46. Zhang WV, D'Esposito F, Edwards RJ, Ramzan I, and Murray M (2008) Interindividual variation in relative CYP1A2/3A4 phenotype influences susceptibility of clozapine oxidation to cytochrome P450-specific inhibition in human hepatic microsomes. Drug Metab Dispos 36: 2547-2555.