Determination of a degradation constant for CYP3A4 by direct suppression of mRNA in a novel human hepatocyte model, HepatoPac

Drug Metabolism and Disposition

Volumn 43, Issue 9, 2015, Pages 1307-1315

  Ramsden, Diane ^a   Zhou, Jin ^a   Tweedie, Donald J ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; GLUCURONOSYLTRANSFERASE 1A1; INTERLEUKIN 6; MESSENGER RNA; MULTIDRUG RESISTANCE PROTEIN 1; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450 3A; SMALL INTERFERING RNA;

ADULT; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME DEGRADATION; ENZYME STABILITY; ENZYME SYNTHESIS; FEMALE; GENE REPRESSION; HALF LIFE TIME; HUMAN; HUMAN CELL; IN VITRO STUDY; MALE; MESSENGER RNA SYNTHESIS; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; RNA DEGRADATION; CELL CULTURE; ENZYMOLOGY; KINETICS; LIVER CELL; METABOLISM; MIDDLE AGED; YOUNG ADULT;

ADULT; CELLS, CULTURED; CYTOCHROME P-450 CYP3A; ENZYME STABILITY; FEMALE; HALF-LIFE; HEPATOCYTES; HUMANS; INTERLEUKIN-6; KINETICS; MALE; MIDDLE AGED; RNA, MESSENGER; RNA, SMALL INTERFERING; YOUNG ADULT;

EID: 84940398340     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.115.065326     Document Type: Article

References (58)

1. Chan TS, Yu H, Moore A., Khetani SR, and Tweedie D J (2013) Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac. Drug Metab Dispos 41:2024-2032.
2. Chu V, Einolf H J, Evers R, Kumar G., Moore D, Ripp S, Silva J., Sinha V, Sinz M, and Skerjanec A (2009) In Vitro and in Vivo Induction of Cytochrome P450: a Survey of the Current Practices and Recommendations: a Pharmaceutical Research and Manufacturers of America Perspective. Drug Metab Dispos 37:1339-1354.
3. Davidson MD, Lehrer M, and Khetani SR (2014) Hormone and drug-mediated modulation of glucose metabolism in a microscale model of the human liver. Tissue Eng Part C Methods PMID: 25517416 [published ahead of print].
4. Diaz D, Fabre I, Daujat M., Saint Aubert B, Bories P, Michel H., and Maurel P (1990) Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. Gastroenterology 99: 737-747.
5. Dickmann LJ, Patel SK, Rock D.A., Wienkers LC, and Slatter JG (2011) Effects of interleukin-6 (IL-6) and an anti-IL-6 monoclonal antibody on drug-metabolizing enzymes in human hepa-tocyte culture. Drug Metab Dispos 39:1415-1422.
6. Einolf HJ (2007) Comparison of different approaches to predict metabolic drug-drug interactions. Xenobiotica 37:1257-1294.
7. Elbashir SM, Harborth J, Lendeckel W., Yalcin A, Weber K, and Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411: 494-498.
8. EMA. European Medicines Agency; Committee for Human Medicinal Products (CHMP); Guideline on the Investigation of Drug interactions. http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2012/07/WC500129606.pdf. 2012. 6-30-2015.
9. FDA. Guidance for Industry: Drug Interaction Studies-Study Design, Data Analysis, Implications for Dosing and Labeling Recommendations (Draft). http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm292362.pdf. 2012. 6-30-2015.
10. Fenneteau F, Poulin P, and Nekka F (2010) Physiologically based predictions of the impact of inhibition of intestinal and hepatic metabolism on human pharmacokinetics of CYP3A substrates. J Pharm Sci 99:486-514.
11. Fire A, Xu S, Montgomery M.K., Kostas SA, Driver SE, and Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806-811.
12. Friedman EJ, Fraser IP, Wang Y.H., Bergman AJ, Li CC, Larson PJ, Chodakewitz J, Wagner J.A., and Stoch SA (2011) Effect of different durations and formulations of diltiazem on the singledose pharmacokinetics of midazolam: how long do we go? J Clin Pharmacol 51:1561-1570.
13. Fromm MF, Busse D, Kroemer H.K., and Eichelbaum M (1996) Differential induction of pre-hepatic and hepatic metabolism of verapamil by rifampin. Hepatology 24:796-801.
14. Galetin A, Burt H, Gibbons L., and Houston JB (2006) Prediction of time-dependent CYP3A4 drug-drug interactions: impact of enzyme degradation, parallel elimination pathways, and intestinal inhibition. Drug Metab Dispos 34:166-175.
15. Giragossian C, LaPerle J, Kosa R.E., and Gillian S (2009) Impact of time-dependent inactivation on the estimation of enzyme kinetic parameters for midazolam. Drug Metab Lett 3:45-53.
16. Grimm SW, Einolf HJ, Hall S.D., He K., Lim HK, Ling KH, Lu C, Nomeir A.A., Seibert E., and Skordos KW, et al. (2009) The conduct of in vitro studies to address time-dependent inhibition of drug-metabolizing enzymes: a perspective of the pharmaceutical research and manufacturers of America. Drug Metab Dispos 37:1355-1370.
17. Guengerich FP (2003) Cytochromes P450, drugs, and diseases. Mol Interv 3:194-204.
18. Hamilton GA, Jolley SL, Gilbert D, Coon D.J., Barros S., and LeCluyse EL (2001) Regulation of cell morphology and cytochrome P450 expression in human hepatocytes by extracellular matrix and cell-cell interactions. Cell Tissue Res 306:85-99.
19. Hammond SM, Bernstein E, Beach D., and Hannon GJ (2000) An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404:293-296.
20. Hargrove JL and Schmidt FH (1989) The role of mRNA and protein stability in gene expression. FASEB J 3:2360-2370.
21. Hewitt NJ, Lechón MJ, Houston J.B., Hallifax D., Brown HS, Maurel P, Kenna JG, Gustavsson L, Lohmann C., and Skonberg C, et al. (2007) Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev 39:159-234.
22. Honig PK, Wortham DC, Zamani K, Conner D.P., Mullin JC, and Cantilena LR (1993) Terfenadine-Ketoconazole Interaction. Pharmacokinetic and Electrocardiographic Consequences. JAMA 269:1513-1518.
23. Hsu A, Granneman GR, Witt G, Locke C., Denissen J, Molla A, Valdes J., Smith J, Erdman K, and Lyons N, et al. (1997) Multiple-dose pharmacokinetics of ritonavir in human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother 41:898-905.
24. Khetani SR and Bhatia SN (2008) Microscale culture of human liver cells for drug development. Nat Biotechnol 26:120-126.
25. Lai AA, Levy RH, and Cutler RE (1978) Time-course of interaction between carbamazepine and clonazepam in normal man. Clin Pharmacol Ther 24:316-323.
26. Lamba JK, Lin YS, Schuetz E.G., and Thummel KE (2002) Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 54:1271-1294.
27. LeCluyse EL (2001) Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur J Pharm Sci 13:343-368.
28. Li Y, Zhou J, Ramsden D., Taub ME, O'Brien D, Xu J, Busacca C.A., Gonnella N., and Tweedie DJ (2014) Enzyme-transporter interplay in the formation and clearance of abundant metabolites of faldaprevir found in excreta but not in circulation. Drug Metab Dispos 42:384-393.
29. Lin YS, Dowling AL, Quigley S.D., Farin FM, Zhang J, Lamba J, Schuetz E.G., and Thummel KE (2002) Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism. Mol Pharmacol 62:162-172.
30. Magnusson MO, Dahl ML, Cederberg J, Karlsson M.O., and Sandström R (2008) Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin. Clin Pharmacol Ther 84:52-62.
31. Mayhew BS, Jones DR, and Hall SD (2000) An in vitro model for predicting in vivo inhibition of cytochrome P450 3A4 by metabolic intermediate complex formation. Drug Metab Dispos 28: 1031-1037.
32. Minematsu T, Lee J, Zha J., Moy S, Kowalski D, Hori K., Ishibashi K, Usui T, and Kamimura H (2010) Time-dependent inhibitory effects of (1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylvinyl-23,25-dimethoxy-13,19,21,27-tetramethyl-17-(2-oxopropyl)-11,28-dioxa-4-azatricyclo[22.3.1.0(4.9)] octacos-18-ene-2,3,10,16-tetrone (FK1706), a novel nonimmunosuppressive immuno-philin ligand, on CYP3A4/5 activity in humans in vivo and in vitro. Drug Metab Dispos 38: 249-259.
33. Morgan ET (1997) Regulation of cytochromes P450 during inflammation and infection. Drug Metab Rev 29:1129-1188.
34. Morgan ET (2001) Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos 29:207-212.
35. Morgan ET, Goralski KB, Piquette-Miller M, Renton K.W., Robertson GR, Chaluvadi MR, Charles KA, Clarke S.J., Kacevska M., and Liddle C, et al. (2008) Regulation of drug-metabolizing enzymes and transporters in infection, inflammation, and cancer. Drug Metab Dispos 36:205-216.
36. Obach RS, Walsky RL, 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.
37. Ogu CC and Maxa JL (2000) Drug interactions due to cytochrome P450. Proc (Bayl Univ Med Cent) 13:421-423 Bayl Univ Med Cent.
38. Paine MF, Khalighi M, Fisher J.M., Shen DD, Kunze KL, Marsh CL, Perkins J.D., and Thummel KE (1997) Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 283:1552-1562.
39. Pichard-Garcia L., Gerbal-Chaloin S, Ferrini J.B., Fabre JM, and Maurel P (2002) Use of long-term cultures of human hepatocytes to study cytochrome P450 gene expression. Methods Enzymol 357:311-321.
40. Quinney SK, Zhang X, Lucksiri A., Gorski JC, Li L, and Hall SD (2010) Physiologically based pharmacokinetic model of mechanism-based inhibition of CYP3A by clarithromycin. Drug Metab Dispos 38:241-248.
41. Ramsden D, Tweedie DJ, Chan T.S., Taub ME, and Li Y (2014a) Bridging in vitro and in vivo metabolism and transport of faldaprevir in human using a novel cocultured human hepatocyte system, HepatoPac. Drug Metab Dispos 42:394-406.
42. Ramsden D, Tweedie DJ, Chan T.S., and Tracy TS (2014b) Altered CYP2C9 activity following modulation of CYP3A4 levels in human hepatocytes: an example of protein-protein interactions. Drug Metab Dispos 42:1940-1946.
43. Ramsden D, Tweedie DJ, St George R, Chen LZ, and Li Y (2014c) Generating an in vitro-in vivo correlation for metabolism and liver enrichment of a hepatitis C virus drug, faldaprevir, using a rat hepatocyte model (HepatoPac). Drug Metab Dispos 42:407-414.
44. Renwick AB, Watts PS, Edwards R.J., Barton PT, Guyonnet I, Price RJ, Tredger J.M., Pelkonen O., Boobis AR, and Lake BG (2000) Differential maintenance of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab Dispos 28:1202-1209.
45. Rodríguez-Antona C., Donato MT, Boobis A, Edwards R.J., Watts PS, Castell JV, and Gómez-Lechón MJ (2002) Cytochrome P450 expression in human hepatocytes and hepatoma cell lines: molecular mechanisms that determine lower expression in cultured cells. Xenobiotica 32: 505-520.
46. Scherr M, Morgan MA, and Eder M (2003) Gene silencing mediated by small interfering RNAs in mammalian cells. Curr Med Chem 10:245-256.
47. Tran JQ, Kovacs SJ, McIntosh T.S., Davis HM, and Martin DE (1999) Morning spot and 24-hour urinary 6 beta-hydroxycortisol to cortisol ratios: intraindividual variability and correlation under basal conditions and conditions of CYP 3A4 induction. J Clin Pharmacol 39:487-494.
48. Venkatakrishnan K and Obach RS (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.
49. Wang WW, Khetani SR, Krzyzewski S, Duignan D.B., and Obach RS (2010) Assessment of a micropatterned hepatocyte coculture system to generate major human excretory and circulating drug metabolites. Drug Metab Dispos 38:1900-1905.
50. Wang YH (2010) Confidence assessment of the Simcyp time-based approach and a static mathematical model in predicting clinical drug-drug interactions for mechanism-based CYP3A inhibitors. Drug Metab Dispos 38:1094-1104.
51. Wong SG (2011) Prediction of Drug-Drug Interactions Arising From Mechanism-Based In-activation: Key Input Parameters and Impact on Risk Assessment. Curr Drug Metab 12: 871-890.
52. Wrighton SA, Brian WR, Sari M.A., Iwasaki M., Guengerich FP, Raucy JL, Molowa DT and Vandenbranden M (1990) Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3). Mol Pharmacol 38:207-213.
53. Wrighton SA, Schuetz EG, Thummel K.E., Shen DD, Korzekwa KR, and Watkins PB (2000) The human CYP3A subfamily: practical considerations. Drug Metab Rev 32:339-361.
54. Yamashita F, Sasa Y, Yoshida S., Hisaka A, Asai Y, Kitano H., Hashida M, and Suzuki H (2013) Modeling of rifampicin-induced CYP3A4 activation dynamics for the prediction of clinical drug-drug interactions from in vitro data. PLoS ONE 8:e70330.
55. Yang J, Liao M, Shou M., Jamei M, Yeo KR, Tucker G.T., and Rostami-Hodjegan A (2008) Cytochrome p450 turnover: regulation of synthesis and degradation, methods for determining rates, and implications for the prediction of drug interactions. Curr Drug Metab 9: 384-394.
56. Yu AM (2007) Small interfering RNA in drug metabolism and transport. Curr Drug Metab 8: 700-708.
57. Zhao P, Zhang L, Grillo J.A., Liu Q., Bullock JM, Moon YJ, Song P, Brar S.S., Madabushi R., and Wu TC, et al. (2011) Applications of physiologically based pharmacokinetic (PBPK) modeling and simulation during regulatory review. Clin Pharmacol Ther 89:259-267.
58. Zhou P (2004) Determining protein half-lives. Methods Mol Biol 284:67-77.