Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: Evaluation of approach to predict the contribution of multiple CYPs

Drug Metabolism and Disposition

Volumn 27, Issue 12, 1999, Pages 1381-1391

  Nakajima, Miki ^a   Nakamura, Sumika ^a   Tokudome, Shogo ^b   Shimada, Noriaki ^c   Yamazaki, Hiroshi ^a   Yokoi, Tsuyoshi ^a  

^a KANAZAWA UNIVERSITY   (Japan)

^b Tokyo Medical Examiner's Office   (Japan)

^c DAIICHI PURE CHEMICALS CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

AZELASTINE; BUFURALOL; CHLORZOXAZONE; COUMARIN ANTICOAGULANT; CYTOCHROME P450; DRUG METABOLITE; ERYTHROMYCIN; FLUVOXAMINE; FURAFYLLINE; KETOCONAZOLE; MEPHENYTOIN; QUINIDINE; SULFAPHENAZOLE; TESTOSTERONE DERIVATIVE;

ARTICLE; CONTROLLED STUDY; DEMETHYLATION; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME KINETICS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; LIVER MICROSOME; PRIORITY JOURNAL;

ANIMALS; B-LYMPHOCYTES; BACULOVIRIDAE; CYTOCHROME P-450 CYP1A2; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; INSECTS; METHYLATION; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; PHTHALAZINES; TRANSFECTION; TUMOR CELLS, CULTURED;

EID: 0032701770     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (41)

1. Adusumalli VE, Wong KK, Kucharczyk N and Sofia RD (1992) Pharmacokinetics of azelastine and its active metabolite, desmethylazelastine, in guinea pigs. Drug Metab Dispos 20:530-535.
2. Arlotto MP, Trant JM and Estabrook RW (1991) Measurement of steroid hydroxylation reactions by high-performance liquid chromatography as indicator of P450 identity and function. Methods Enzymol 206:454-462.
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. Becquemont L, Le Bot MA, Riche C, Funck-Brentano C, Jaillon P and Beaune P (1998) Use of heterologously expressed human cytochrome P450 1A2 to predict tacrine-fluvoxamine drug interaction in man. Pharmacogenetics 8:101-108.
5. Broly F, Libersa C, Lhermitte M, Bechtel P and Dupuis B (1989) Effect of quinidine on the dextromethorphan O-demethylase activity of microsomal fractions from human liver. Br J Clin Pharmacol 28:29-36.
6. Chiba K, Kobayashi K, Manabe K, Tani M, Kamataki T and Ishizaki T (1993) Oxidative metabolism of omeprazole in human liver microsomes: Cosegregation with S-mephenytoin 4′-hydroxylation. J Pharmacol Exp Ther 266:52-59.
7. Crespi CL (1995) Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research. Adv Drug Res 26:179-235.
8. Gillam EMJ, Guo Z, Ueng Y-F, Yamazaki H, Cock I, Reilly PEB, Hooper WD and Guengerich FP (1995) Expression of cytochrome P450 3A5 in Escherichia coli: Effects of 5′ modification, purification, spectral characterization, reconstitution conditions, and catalytic activities. Arch Biochem Biophys 317:374-384.
9. Hazama H, Nakajima T, Hisada T, Hamada E, Omata M and Kurachi Y (1994) Effects of azelastine on membrane currents in tracheal smooth muscle cells isolated from the guinea-pig. Eur J Pharmacol 259:143-150.
10. Inoue K, Yamazaki H, Imiya K, Akasaka S, Guengerich FP and Shimada T (1997) Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methylhydroxylation and S-mephenytoin 4′-hydroxylation activities in livers of Japanese and Caucasian populations. Pharmacogenetics 7:103-113.
11. Iwatsubo T, Hirota N, Ooie T, Suzuki H, Shimada N, Chiba K, Ishizaki T, Green CE, Tyson CA and Sugiyama Y (1997) Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data. Pharmacol Ther 73:147-171.
12. Johannesen KAM and Depierre JW (1978) Measurement of cytochrome P-450 in the presence of large amounts of contaminating hemoglobin and methemoglobin. Anal Biochem 86:725-732.
13. 5 and cytochrome P-450 and aniline-induced P-450 difference spectrum. Jpn J Pharmacol 24:195-203.
14. 5 for maximum activity. Biochem Pharmacol 17:2479-2483.
15. Kobayashi K, Chiba K, Yagi T, Shimada N, Taniguchi T, Horie T, Tani M, Yamamoto T, Ishizaki T and Kuroiwa Y (1997) Identification of cytochrome P450 isoforms involved in citalopram N-demethylation by human liver microsomes. J Pharmacol Exp Ther 280:927-933.
16. Kronbach T, Mathys D, Gut J, Catin T and Meyer UA (1987) High-performance liquid chromatographic assays for bufuralol 1′-hydroxylase, debrisoquine 4-hydroxylase, and dextromethorphan O-demethylase in microsomes and purified cytochrome P-450 isozymes of human liver. Anal Biochem 162:24-32.
17. Lowry OH, Rosebrough NJ, Farr AL and Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265-275.
18. McManus ME, Burgess WM, Veronese ME, Huggett A, Quattrochi LC and Tuley RH (1990) Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochromes P-450. Cancer Res 50:3367-3376.
19. Morganroth J, Lyness WH, Perhach JL, Mather GG, Harr JE, Trager WF, Levy RH and Rosenberg A (1997) Lack of effect of azelastine and ketoconazole coadministration on electrocardiographic parameters in healthy volunteers. J Clin Pharmacol 37:1065-1072.
20. Muck W (1994) Pharmacokinetic drug interaction, in Drug Interactions Studies During Drug Development (Kuhlmann J ed) pp 50-54, W. Zuckschwerdt Verlag, Munich.
21. Nakajima M, Kobayashi K, Shimada N, Tokudome S, Yamamoto T and Kuroiwa Y (1998) Involvement of CYP1A2 in mexiletine metabolism. Br J Clin Pharmacol 46:55-62.
22. Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC and Neben DW (1996) P450 superfamily: Update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6:1-42.
23. Pastrakuljic A, Tang BK, Roberts EA and Kalow W (1997) Distinction of CYP1A1 and CYP1A2 activity by selective inhibition using fluvoxamine and isosafrole. Biochem Pharmacol 53: 531-538.
24. Perhach JL, Chand N, Diamantis W, Sofia RD and Rosenberg A (1989) Azelastine: A novel oral antiasthma compound with several modes of action, in Allergy and Asthma. New Trends and Approaches to Therapy (Kad AB ed) pp 230-248, Blackwell Scientific Publications, Oxford, London.
25. Peter R, Böcker R, Beaune PH, Iwasaki M, Guengerich FP and Yang CS (1990) Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450 IIE1. Chem Res Toxicol 3:566-573.
26. Pivonka J, Segelman FH, Hartman CA, Segl WE, Kucharczyk N and Sofia RD (1987) Determination of azelastine and desmethylazelastine in human plasma by high-performance liquid chromatography. J Chromatogr 420:89-98.
27. 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, carcinogenes and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423.
28. Sinjari T, Törnwall U and Darnerud PO (1993) Induction of 7-ethoxyresorurm-O-deethylase (EROD) activity in mice foetuses by the PCB-congener 3,3′,4,4′-tetrachlorobiphenyl. Xenobiotica 23:107-114.
29. Spatzenegger M and Jaeger W (1995) Clinical importance of hepatic cytochrome P450 in drug metabolism. Drug Metab Rev 27:397-417.
30. Szelenyi L (1989) Pharmacological profile of azelastine. Drug Today 25:3-8.
31. Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH and Miners JO (1994) Direct characterization of the selectivity of furafylline as an inhibitor of human cytochromes P450 1A1 and 1A2. Pharmacogenetics 4:281-284.
32. Tatsumi K, Ou T, Yamada H and Yoshimura H (1980) Studies on metabolic fate of a new antiallergic agent, azelastine (4-(p-chlorobenzyl)-2-[N-methylperhydroazepinyl-(4)]-1-(2/H)-phthalazinone hydrochloride). Jpn J Pharmacol 30:37-48.
33. Tatsumi K, Yamada H, Yoshimura H. Nishizawa Y, Sakai M, Mizuo H and Yamato C (1984) Metabolism of an antiallergic agent, azelastine (4-(p-chlorobenzyl)-2-[N-methylperhydroazepinyl-(4)]-1-(2H)-phthalazinone hydrochloride) in rats and guinea pigs. Hiroshima J Med Sci 33:669-678.
34. Watkins PB, Wrighton SA, Maurel P, Schuetz EG, Mendez-Picon G, Parker GA and Guzelian PS (1985) Identification of an inducible form of cytochrome P-450 in human liver. Proc Natl Acad Sci USA 82:6310-6314.
35. Waxman DJ, Attisano C, Guengerich FP and Lapenson DP (1988) Human liver microsomal steroid metabolism: Identification of the major microsomal steroid hormone 6β-hydroxylase cytochrome P-450 enzyme. Arch Biochem Biophys 263:424-436.
36. Yamazaki H, Guo Z, Persmark M, Mimura M, Inoue K, Guengerich FP and Shimada T (1994) Bufuralol hydroxylation by cytochrome P450 2D6 and 1A2 enzymes in human liver microsomes. Mol Pharmacol 46:568-577.
37. Yamazaki H, Inoue K, Shaw PM, Checovich WJ, Guengerich FP and Shimada T (1997) Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: Effects of contents of these two forms in individual human samples. J Pharmacol Exp Ther 283:434-442.
38. 5. J Biol Chem 271:27438-27444.
39. 5 in the oxidation of testosterone and nifedipine by recombinant cytochrome P450 3A4 and by human liver microsomes. Arch Biochem Biophys 325:174-182.
40. 14C]azelastine in guinea pigs. Drug Metab Dispos 20:536-540.
41. Yun C-H, Shimada T and Guengerich FP (1991) Purification and characterization of human liver microsomal cytochrome P-450 2A6. Mol Pharmacol 40:679-685.