An intestinal epithelium-specific cytochrome P450 (P450) reductase-knockout mouse model: Direct evidence for a role of intestinal P450s in first-pass clearance of oral nifedipine

Drug Metabolism and Disposition

Volumn 37, Issue 3, 2009, Pages 651-657

  Zhang, Qing Yu ^a,b   Fang, Cheng ^a   Zhang, Jin ^a   Dunbar, Deborah ^a   Kaminsky, Laurence ^a   Ding, Xinxin ^a  

^a STATE UNIVERSITY OF NEW YORK   (United States)

^b WADSWORTH CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 1A1; CYTOCHROME P450 2B; CYTOCHROME P450 2C; CYTOCHROME P450 3A; CYTOCHROME P450 REDUCTASE; NIFEDIPINE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; ENZYME ACTIVITY; FIRST PASS EFFECT; HISTOLOGY; IMMUNOHISTOCHEMISTRY; INTESTINE ABSORPTION; INTESTINE EPITHELIUM CELL; KNOCKOUT MOUSE; MALE; MAXIMUM PLASMA CONCENTRATION; MICROSOME; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ANIMALS; AREA UNDER CURVE; CALCIUM CHANNEL BLOCKERS; IMMUNOHISTOCHEMISTRY; INTESTINAL MUCOSA; MICE; MICE, KNOCKOUT; NADPH-FERRIHEMOPROTEIN REDUCTASE; NIFEDIPINE;

MUS;

EID: 61449095680     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.108.025429     Document Type: Article

References (36)

1. Bailey DG, Spence JD, Munoz C, and Arnold JM (1991) Interaction of citrus juices with felodipine and nifedipine. Lancet 337:268-269.
2. Chen Y, Liu YQ, Su T, Ren X, Shi L, Liu D, Gu J, Zhang QY, and Ding X (2003) Immunoblot analysis and immunohistochemical characterization of CYP2A expression in human olfactory mucosa. Biochem Pharmacol 66:1245-1251.
3. Ding X and Kaminsky LS (2003) Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu Rev Pharmacol Toxicol 43:149-173.
4. Doherty MM and Charman WN (2002) The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism? Clin Pharmacokinet 41:235-253.
5. el Marjou F, Janssen KP, Chang BH, Li M, Hindie V, Chan L, Louvard D, Chambon P, Metzger D, and Robině S (2004) Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis 39:186-193.
6. Fang C, Gu J, Xie F, Behr M, Yang W, Abel ED, and Ding X (2008) Deletion of the NADPH-cytochrome P450 reductase gene in cardiomyocytes does not protect mice against doxorubicin-mediated acute cardiac toxicity. Drug Metab Dispos 36:1722-1728.
7. Fasco MJ, Silkworth JB, Dunbar DA, and Kaminsky LS (1993) Rat small intestinal cytochromes P450 probed by warfarin metabolism. Mol Pharmacol 43:226-233.
8. Finn RD, McLaren AW, Carrie D, Henderson CJ, and Wolf CR (2007) Conditional deletion of cytochrome P450 oxidoreductase in the liver and gastrointestinal tract: a new model for studying the functions of the P450 system. J Pharmacol Exp Ther 322:40-47.
9. Grundy JS, Eliot LA, and Foster RT (1997) Extrahepatic first-pass metabolism of nifedipine in the rat. Biopharm Drug Dispos 18:509-522.
10. Gu J, Chen CS, Wei Y, Fang C, Xie F, Kannan K, Yang W, Waxman DJ, and Ding X (2007) A mouse model with liver-specific deletion and global suppression of the NADPH-cytochrome P450 reductase gene: characterization and utility for in vivo studies of cyclophosphamide disposition. J Pharmacol Exp Ther 321:9-17.
11. Gu J, Weng Y, Zhang QY, Cui H, Behr M, Wu L, Yang W, Zhang L, and Ding X (2003) Liver-specific deletion of the NADPH-cytochrome P450 reductase gene: impact on plasma cholesterol homeostasis and the function and regulation of microsomal cytochrome P450 and heme oxygenase. J Biol Chem 278:25895-25901.
12. Guengerich FP, Martin MV, Beaune PH, Kremers P, Wolff T, and Waxman DJ (1986) Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. J Biol Chem 261:5051-5060.
13. Hem A, Smith AJ, and Solberg P (1998) Saphenous vein puncture for blood sampling of the mouse, rat, hamster, gerbil, guinea pig, ferret and mink. Lab Anim 32:364-368.
14. Henderson CJ, Otto DM, Carrie D, Magnuson MA, McLaren AW, Rosewell I, and Wolf CR (2003) Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase. J Biol Chem 278:13480-13486.
15. Holtbecker N, Fromm MF, Kroemer HK, Ohnhaus EE, and Heidemann H (1996) The nifedipinerifampin interaction. Evidence for induction of gut wall metabolism. Drug Metab Dispos 24:1121-1123.
16. Ito S, Chen C, Satoh J, Yim S, and Gonzalez FJ (2007) Dietary phytochemicals regulate whole-body CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator-dependent system in gut. J Clin Invest 117:1940-1950.
17. Jankowski A and Lamparczyk H (1994) Evaluation of chromatographic methods for the determination of nifedipine in human serum. J Chromatogr A 668:469-473.
18. Kaminsky LS and Fasco MJ (1991) Small intestinal cytochromes P450. Crit Rev Toxicol 21:407-422.
19. Kaminsky LS and Zhang QY (2003) The small intestine as a xenobiotic-metabolizing organ. Drug Metab Dispos 31:1520-1525.
20. Madison BB, Dunbar L, Qiao XT, Braunstein K, Braunstein E, and Gumucio DL (2002) Cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine. J Biol Chem 277:33275-33283.
21. Maunoury R, Robině S, Pringault E, Léonard N, Gaillard JA, and Louvard D (1992) Developmental regulation of villin gene expression in the epithelial cell lineages of mouse digestive and urogenital tracts. Development 115:717-728.
22. Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, and Nebert DW (2004) Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics 14:1-18.
23. Paine MF, Hart HL, Ludington SS, Haining RL, Rettie AE, and Zeldin DC (2006) The human intestinal cytochrome P450 "pie." Drug Metab Dispos 34:880-886.
24. Paine MF and Oberlies NH (2007) Clinical relevance of the small intestine as an organ of drug elimination: drug-fruit juice interactions. Expert Opin Drug Metab Toxicol 3:67-80.
25. Suzuki H and Sugiyama Y (2000) Role of metabolic enzymes and efflux transporters in the absorption of drugs from the small intestine. Eur J Pharm Sci 12:3-12.
26. Thummel KE, Kunze KL, and Shen DD (1997) Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction. Adv Drug Deliv Rev 27:99-127.
27. van Herwaarden AE, Wagenaar E, van der Kruijssen CM, van Waterschoot RA, Smit JW, Song JY, van der Valk MA, van Tellingen O, van der Hoorn JW, Rosing H, et al. (2007) Knockout of cytochrome P450 3A yields new mouse models for understanding xenobiotic metabolism. J Clin Invest 117:3583-3592.
28. van Waterschoot RA, van Herwaarden AE, Lagas JS, Sparidans RW, Wagenaar E, van der Kruijssen CM, Goldstein JA, Zeldin DC, Beijnen JH, and Schinkel AH (2008) Midazolam metabolism in cytochrome P450 3A knockout mice can be attributed to up-regulated CYP2C enzymes. Mol Pharmacol 73:1029-1036.
29. Weng Y, DiRusso CC, Reilly AA, Black PN, and Ding X (2005) Hepatic gene expression changes in mouse models with liver-specific deletion or global suppression of the NADPH-cytochrome P450 reductase gene. Mechanistic implications for the regulation of microsomal cytochrome P450 and the fatty liver phenotype. J Biol Chem 280:31686-31698.
30. Weng Y, Fang C, Turesky RJ, Behr M, Kaminsky LS, and Ding X (2007) Determination of the role of target tissue metabolism in lung carcinogenesis using conditional cytochrome P450 reductase-null mice. Cancer Res 67:7825-7832.
31. Wu CY and Benet LZ (2005) Predicting drug disposition via application of BCS: transport/ absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res 22:11-23.
32. Wu L, Gu J, Cui H, Zhang QY, Behr M, Fang C, Weng Y, Kluetzman K, Swiatek PJ, Yang W, et al. (2005) Transgenic mice with a hypomorphic NADPH-cytochrome P450 reductase gene: effects on development, reproduction, and microsomal cytochrome P450. J Pharmacol Exp Ther 312:35-43.
33. Wu L, Gu J, Weng Y, Kluetzman K, Swiatek P, Behr M, Zhang QY, Zhuo X, Xie Q, and Ding X (2003) Conditional knockout of the mouse NADPH-cytochrome P450 reductase gene. Genesis 36:177-181.
34. Yoshisue K, Nagayama S, Shindo T, and Kawaguchi Y (2001) Effects of 5-fluorouracil on the drug-metabolizing enzymes of the small intestine and the consequent drug interaction with nifedipine in rats. J Pharmacol Exp Ther 297:1166-1175.
35. Zhang QY, Dunbar D, and Kaminsky LS (2003) Characterization of mouse small intestinal cytochrome P450 expression. Drug Metab Dispos 31:1346-1351.
36. Zhang QY, Kaminsky LS, Dunbar D, Zhang J, and Ding X (2007) Role of small intestinal cytochrome P450 in the bioavailability of oral nifedipine. Drug Metab Dispos 35:1617-1623.