Irreversible enzyme inhibition kinetics and drug-drug interactions

Methods in Molecular Biology

Volumn 1113, Issue , 2014, Pages 57-91

  Mohutsky, Michael ^a   Hall, Stephen D ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Drug drug interaction; Enzyme inactivation; Heme; Mechanism based inhibition; Metabolite intermediate complex; Suicide inhibition; Time dependent inhibition

Indexed keywords

APOPROTEIN; DRUG METABOLIZING ENZYME; ENZYME INHIBITOR; HEME;

ARTICLE; CONCEPTUAL FRAMEWORK; DRUG HALF LIFE; DRUG INTERACTION; ENZYME ASSAY; ENZYME INACTIVATION; ENZYME INHIBITION; ENZYME KINETICS; HUMAN; IC 50; IN VITRO STUDY; IN VIVO STUDY; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PROTEIN MODIFICATION;

CYTOCHROME P-450 ENZYME SYSTEM; DRUG DESIGN; DRUG INTERACTIONS; ENZYME INHIBITORS; ENZYMES; HUMANS; KINETICS;

EID: 84934443116     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-62703-758-7_5     Document Type: Article

References (100)

1. Renton KW (1985) Inhibition of hepatic microsomal drug metabolism by the calcium channel blockers diltiazem and verapamil. Biochem Pharmacol 34(14):2549-2553, 0006-2952(85)90541-6 [pii]
2. Mousa O, Brater DC, Sunblad KJ, Hall SD (2000) The interaction of diltiazem with simvastatin. Clin Pharmacol Ther 67 (3):267-274. doi:10.1067/mcp.2000. 104609, S0009923600965603 [pii]
3. Jones DR, Gorski JC, Hamman MA, Mayhew BS, Rider S, Hall SD (1999) Diltiazem inhibition of cytochrome P-450 3A activity is due to metabolite intermediate complex formation. J Pharmacol Exp Ther 290 (3):1116-1125
4. Sutton D, Butler AM, Nadin L, Murray M (1997) Role of CYP3A4 in human hepatic diltiazem N-demethylation: Inhibition of CYP3A4 activity by oxidized diltiazem metabolites. J Pharmacol Exp Ther 282 (1):294-300
5. Zhang X, Quinney SK, Gorski JC, Jones DR, Hall SD (2009) Semiphysiologically based pharmacokinetic models for the inhibition of midazolam clearance by diltiazem and its major metabolite. Drug Metab Dispos 37 (8):1587-1597. doi:10.1124/dmd.109. 026658, dmd.109.026658 [pii]
6. Zhang X, Jones DR, Hall SD (2009) Prediction of the effect of erythromycin, diltiazem, and their metabolites, alone and in combination, on CYP3A4 inhibition. Drug Metab Dispos 37(1):150-160. doi:10.1124/dmd. 108.022178, dmd.108.022178 [pii]
7. Rowland Yeo K, Jamei M, Yang J, Tucker GT, Rostami-Hodjegan A (2012) Physiologically based mechanistic modelling to predict complex drug-drug interactions involving simultaneous competitive and time-dependent enzyme inhibition by parent compound and its metabolite in both liver and gut-The effect of diltiazem on the time-course of exposure to triazolam. Eur J Pharm Sci 39(5):298-309. doi:10.1016/j.ejps.2009.12.002, S0928-0987(09)00358-3 [pii]
8. Gascon M-P, Dayer P (1991) In vitro forecasting of drugs which may interfere with the biotransformation of midazolam. Eur J Clin Pharmacol 41:573-578
9. Olkkola K, Aranko K, Luurila H, Hiller A, Saarnivaara L, Himberg J-J, Neuvo-nen PJ (1993) A potentially hazardous interaction between erythromycin and midazolam. Clin Pharmacol Ther 53:298-305
10. Freeman J, Martell R, Carrufhers S, Heinrichs D, Keown P, Stiller C (1987) Cyclosporinerythromycin interaction in normal subjects. Br J Clin Pharmacol 23:776-778
11. Bartkowski P, Goldberg M, Larijani G, Boerner T (1989) Inhibition of alfentanil metabolism by erythromycin. Clin Pharmacol Ther 46:99-102
12. Phillips J, Antal E, Smith R (1986) A pharmacokinetic drug interaction between erythromycin and triazolam. J Clin Psychopharmacol 6:297-299
13. Gorski J, Jones D, Hamman M, Wrighton S, Hall S (1999) Biotransformation of alprazolam by members of the human cytochrome P450 3A subfamily. Xenobiotica 29:931-944
14. Wong YY, Ludden TM, Bell RD (1983) Effect of erythromycin on carbamazepine kinetics. Clin Pharmacol Ther 33:460-464
15. Lindstrom T, Hanssen B, Wrighton S (1993) Cytochrome P-450 complex formation by dirithromycin and other macrolides in rat and human livers. Antimicrobial Agents Chemother 37:265-269
16. Larrey D, Funck-Brentano C, Breil P, Vitaux J, Theodore C, Babany G, Pessayre D (1983) Effects of erythromycin on hepatic drugmetabolizing enzymes in humans. Biochem Pharmacol 32(6):1063-1068
17. Pessayre D, Larrey D, Vitaux J, Breil P, Belghiti J, Benhamou JP (1982) Formation of an inactive cytochrome P-450 Fe(II)-metabolite complex after administration of troleandomycin in humans. Biochem Pharmacol 31 (9):1699-1704
18. Zhang X, Galinsky RE, Kimura RE, Quinney SK, Jones DR, Hall SD (2010) Inhibition of CYP3A by erythromycin: In vitro-in vivo correlation in rats. Drug Metab Dispos 38 (1):61-72. doi:10.1124/dmd.109.028290, dmd.109.028290 [pii]
19. Pinto AG, Wang YH, Chalasani N, Skaar T, Kolwankar D, Gorski JC, Liangpunsakul S, Hamman MA, Arefayene M, Hall SD (2005) Inhibition of human intestinal wall metabolism by macrolide antibiotics: Effect of clarithromycin on cytochrome P450 3A4/5 activity and expression. Clin Pharmacol Ther 77(3):178-188. doi:10.1016/j.clpt.2004. 10.002, S000992360400342X [pii]
20. Pinto AG, Horlander J, Chalasani N, Hamman M, Asghar A, Kolwankar D, Hall SD (2005) Diltiazem inhibits human intestinal cytochrome P450 3A (CYP3A) activity in vivo without altering the expression of intestinal mRNA or protein. Br J Clin Pharmacol 59(4):440-446. doi:10.1111/j.1365-2125.2005.02343.x, BCP2343 [pii]
21. Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB (1997) Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest 99(10):2545-2553
22. He K, Iyer KR, Hayes RN, Sinz MW, Woolf TF, Hollenberg PF (1998) Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol 11(4):252-259
23. Malhotra S, Schimiedlin-Ren P, Paine MF, Criss AB, Watkins P (2001) The furocoumarin 60, 70-dihydroxybergamottin (DHB) accelerates CYP3A4 degradation via the ubiquitin-proteasomal pathway. Drug Metab Rev 33:97
24. Guo LQ, Fukuda K, Ohta T, Yamazoe Y (2000) Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity. Drug Metab Dispos 28(7):766-771
25. Arayne MS, Sultana N, Bibi Z (2005) Grape fruit juice-drug interactions. Pak J Pharm Sci 18(4):45-57
26. Grimm SW, Einolf HJ, Hall SD, He K, Lim HK, Ling KH, Lu C, Nomeir AA, Seibert E, Skordos KW, Tonn GR, Van Horn R, Wang RW, Wong YN, Yang TJ, Obach RS (2009) The conduct of in vitro studies to address time-dependent inhibition of drugmetabolizing enzymes: A perspective of the pharmaceutical research and manufacturers of America. Drug Metab Dispos 37 (7):1355-1370. doi:10.1124/dmd.109. 026716, dmd.109.026716 [pii]
27. Bartholow M (2012) Top 200 Drugs of 2011. http://www.pharmacytimes.com/ publications/issue/2012/July2012/Top-200-Drugs-of-2011. Accessed 12/30/2012
28. Cooper CL, van Heeswijk RP, Gallicano K, Cameron DW (2003) A review of low-dose ritonavir in protease inhibitor combination therapy. Clin Infect Dis 36(12):1585-1592. doi:10.1086/375233, CID30655 [pii]
29. Mathias AA, German P, Murray BP, Wei L, Jain A, West S, Warren D, Hui J, Kearney BP (2010) Pharmacokinetics and pharmacodynamics of GS-9350: A novel pharmacokinetic enhancer without anti-HIV activity. Clin Pharmacol Ther 87(3):322-329. doi:10. 1038/clpt.2009.228, clpt2009228 [pii]
30. Singh J, Petter RC, Baillie TA, Whitty A (2011) The resurgence of covalent drugs. Nat Rev Drug Discov 10(4):307-317. doi:10.1038/nrd3410, nrd3410 [pii]
31. Vandenbrink BM, Davis JA, Pearson JT, Foti RS, Wienkers LC, Rock DA (2012) Cytochrome P450 architecture and cysteine nucleophile placement impacts raloxifene mediated mechanism-based inactivation. Mol Pharmacol 82(5):835-842. doi:10.1124/mol.112. 080739, mol.112.080739 [pii]
32. Yamazaki H, Urano T, Hiroki S, Shimada T (1996) Effects of erythromycin and roxithromycin on oxidation of testosterone and nifedipine catalyzed by CYP3A4 in human liver microsomes. J Toxicol Sci 21(4):215-226
33. Wang YH, Jones DR, Hall SD (2005) Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos 33(5):664-671. doi:10. 1124/dmd.104.001834, dmd.104.001834 [pii]
34. Polasek TM, Miners JO (2008) Timedependent inhibition of human drug metabolizing cytochromes P450 by tricyclic antidepressants. Br J Clin Pharmacol 65(1):87-97. doi:10.1111/j.1365-2125.2007.02964.x, BCP2964 [pii]
35. Hanson KL, VandenBrink BM, Babu KN, Allen KE, Nelson WL, Kunze KL (2010) Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: Opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (s)-fluoxetine, and Ndesmethyldiltiazem. Drug Metab Dispos 38 (6):963-972. doi:dmd.110.032391, [pii] 10.1124/dmd.110.032391
36. Franklin R (1977) Inhibition of mixedfunction oxidations by substrates forming reduced cytochrome P-450 metabolicintermediate complexes. Pharmac Ther 2:227-245
37. Bertelsen KM, Venkatakrishnan K, Von Moltke LL, Obach RS, Greenblatt DJ (2003) Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: Comparison with fluoxetine and quinidine. Drug Metab Dispos 31(3):289-293
38. Heydari A, Yeo KR, Lennard MS, Ellis SW, Tucker GT, Rostami-Hodjegan A (2004) Mechanism-based inactivation of CYP2D6 by methylenedioxymethamphetamine. Drug Metab Dispos 32(11):1213-1217, 10.1124/dmd.104.001180dmd.104.001180 [pii]
39. Salminen KA, Meyer A, Imming P, Raunio H (2011) CYP2C19 progress curve analysis and mechanism-based inactivation by three methylenedioxyphenyl compounds. Drug Metab Dispos 39(12):2283-2289. doi:10. 1124/dmd.111.041319, dmd.111.041319 [pii]
40. Hutzler JM, Melton RJ, Rumsey JM, Schnute ME, Locuson CW, Wienkers LC (2006) Inhibition of cytochrome P450 3A4 by a pyrimidineimidazole: Evidence for complex heme interactions. Chem Res Toxicol 19 (12):1650-1659. doi:10.1021/tx060198m
41. Iwata H, Tezuka Y, Kadota S, Hiratsuka A, Watabe T (2004) Identification and characterization of potent CYP3A4 inhibitors in Schisandra fruit extract. Drug Metab Dispos 32 (12):1351-1358. doi:10.1124/dmd.104. 000646dmd.104.000646 [pii]
42. Usia T, Watabe T, Kadota S, Tezuka Y (2005) Metabolite-cytochrome P450 complex formation by methylenedioxyphenyl lignans of Piper cubeba: Mechanism-based inhibition. Life Sci 76(20):2381-2391. doi:S0024-3205(05) 00033-0, [pii]10.1016/j.lfs.2004.12.005
43. Lopez-Garcia MP, Dansette PM, Mansuy D (1994) Thiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: Inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid. Biochemistry 33(1):166-175
44. Rademacher PM, Woods CM, Huang Q, Szklarz GD, Nelson SD (2012) Differential oxidation of two thiophene-containing regioisomers to reactive metabolites by cytochrome P450 2C9. Chem Res Toxicol 25 (4):895-903. doi:10.1021/tx200519d
45. Jean P, Lopez-Garcia P, Dansette P, Mansuy D, Goldstein JL (1996) Oxidation of tienilic acid by human yeast-expressed cytochromes P-450 2C8, 2C9, 2C18 and 2C19. Evidence that this drug is a mechanism-based inhibitor specific for cytochrome P-450 2C9. Eur J Biochem 241(3):797-804
46. Koenigs LL, Peter RM, Hunter AP, Haining RL, Rettie AE, Friedberg T, Pritchard MP, Shou M, Rushmore TH, Trager WF (1999) Electrospray ionization mass spectrometric analysis of intact cytochrome P450: Identification of tienilic acid adducts to P450 2C9. Biochemistry 38(8):2312-2319. doi:10. 1021/bi9823030bi9823030 [pii]
47. Robin MA, Maratrat M, Le Roy M, Le Breton FP, Bonierbale E, Dansette P, Ballet F, Mansuy D, Pessayre D (1996) Antigenic targets in tienilic acid hepatitis. Both cytochrome P450 2C11 and 2C11-tienilic acid adducts are transported to the plasma membrane of rat hepatocytes and recognized by human sera. J Clin Invest 98(6):1471-1480. doi:10.1172/JCI118936
48. Teng WC, Oh JW, New LS, Wahlin MD, Nelson SD, Ho HK, Chan EC (2010) Mechanism-based inactivation of cytochrome P450 3A4 by lapatinib. Mol Pharmacol 78 (4):693-703. doi:mol.110.065839, [pii] 10.1124/mol.110.065839
49. Chan EC, New LS, Chua TB, Yap CW, Ho HK, Nelson SD (2012) Interaction of lapatinib with cytochrome P450 3A5. Drug Metab Dispos 40(7):1414-1422. doi:dmd.112. 044958 [pii]10.1124/dmd.112.044958
50. Kang P, Liao M,Wester MR, Leeder JS, Pearce RE, Correia MA (2008) CYP3A4-Mediated carbamazepine (CBZ) metabolism: Formation of a covalent CBZ-CYP3A4 adduct and alteration of the enzyme kinetic profile. Drug Metab Dispos 36(3):490-499. doi:dmd.107. 016501, [pii]10.1124/dmd.107.016501
51. Sridar C, D?Agostino J, Hollenberg PF (2012) Bioactivation of the cancer chemopreventive agent tamoxifen to quinone methides by cytochrome P4502B6 and identification of the modified residue on the apoprotein. Drug Metab Dispos. doi:dmd.112.047266 [pii]10. 1124/dmd.112.047266
52. Yukinaga H, Takami T, Shioyama SH, Tozuka Z, Masumoto H, Okazaki O, Sudo K (2007) Identification of cytochrome P450 3A4 modification site with reactive metabolite using linear ion trap-Fourier transform mass spectrometry. Chem Res Toxicol 20 (10):1373-1378. doi:10.1021/tx700165q
53. Guengerich F (1990) Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene. Chem Res Toxicol 3:363-371
54. Guengerich F (1988) Oxidation of 17 aethynylestradiol by human liver cytochrome P-450. Mol Pharmacol 33:500-508
55. Blobaum AL (2006) Mechanism-based inactivation and reversibility: Is there a new trend in the inactivation of cytochrome p450 enzymes Drug Metab Dispos 34(1):1-7, 34/1/1[pii]10.1124/dmd.105.004747
56. Foti RS, Rock DA, Pearson JT,Wahlstrom JL, Wienkers LC (2011) Mechanism-based inactivation of cytochrome P450 3A4 by mibefradil through heme destruction. Drug Metab Dispos 39(7):1188-1195. doi:dmd.111. 038505, [pii]10.1124/dmd.111.038505
57. Mullins ME, Horowitz BZ, Linden DH, Smith GW, Norton RL, Stump J (1998) Life-threatening interaction of mibefradil and beta-blockers with dihydropyridine calcium channel blockers. JAMA 280 (2):157-158. doi:jbr80135 [pii]
58. Amunugama HT, Zhang H, Hollenberg PF (2012) Mechanism-based inactivation of cytochrome P450 2B6 by methadone through destruction of prosthetic heme. Drug Metab Dispos 40(9):1765-1770. doi:dmd.112. 045971, [pii]10.1124/dmd.112.045971
59. Baer BR, DeLisle RK, Allen A (2009) Benzylic oxidation of gemfibrozil-1-O-beta-glucuronide by P450 2C8 leads to heme alkylation and irreversible inhibition. Chem Res Toxicol 22(7):1298-1309. doi:10. 1021/tx900105n
60. Silverman RB (1995) Mechanism-based enzyme inactivators. Methods Enzymol 249:240-283
61. Waley SG (1980) Kinetics of suicide substrates. Biochem J 185(3):771-773
62. Waley SG (1985) Kinetics of suicide substrates. Practical procedures for determining parameters. Biochem J 227(3):843-849
63. Silverman R (1988) Mechanism-based enzyme inactivation: Chemistry and enzymology, vol I. CRC Press, Boca Raton, FL
64. Tatsunami S, Yago N, HosoeM(1981) Kinetics of suicide substrates. Steady-state treatments and computer-aided exact solutions. Biochim Biophys Acta 662:226-235
65. Walsh C, Cromartie T, Marcotte P, Spence R (1978) Suicide substrates for flavoprotein enzymes. Meth Enzymol 53:437-448
66. Bensoussan C, Delaforge M, Mansuy D (1995) Particular ability of cytochromes P450 3A to form inhibitory P450-ironmetabolite complexes upon metabolic oxidation of aminodrugs. Biochem Pharmacol 49:591-602
67. Korzekwa K, Krishnamachary N, Shou M, Ogai A, Parise R, Rettie A, Gonzalez F, Tracy T (1998) Evaluation of atypical cytochrome P450 kinetics with two-substrate models: Evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochem J 37:4137-4147
68. Agency EM (2012) Guideline on the Investigation of Drug Interactions. http://www. ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2012/ 07/WC5 00129606.pdf.
69. Food and Drug Administration CfDEaRC (2012) Guidance for Industry (draft): Drug Interaction Studies-Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations, February 2012. http://www.fda.gov/ downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm292362.pdf. Accessed 4 Sept 2012
70. Henne KR, Tran TB, VandenBrink BM, Rock DA, Aidasani DK, Subramanian R, Mason AK, Stresser DM, Teffera Y, Wong SG, Johnson MG, Chen X, Tonn GR, Wong BK (2012) Sequential metabolism of AMG 487, a novel CXCR3 antagonist, results in formation of quinone reactive metabolites that covalently modify CYP3A4 Cys239 and cause time-dependent inhibition of the enzyme. Drug Metab Dispos 40 (7):1429-1440. doi:dmd.112.045708, [pii] 10.1124/dmd.112.045708
71. Parkinson A, Kazmi F, Buckley DB, Yerino P, Paris BL, Holsapple J, Toren P, Otradovec SM, Ogilvie BW (2011) An evaluation of the dilution method for identifying metabolismdependent inhibitors of cytochrome P450 enzymes. Drug Metab Dispos 39 (8):1370-1387. doi:dmd.111.038596, [pii] 10.1124/dmd.111.038596
72. Zhang ZY,Wong YN (2005) Enzyme kinetics for clinically relevant CYP inhibition. Curr Drug Metab 6(3):241-257
73. Atkinson A, Kenny JR, Grime K (2005) Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis. Drug Metab Dispos 33(11):1637-1647. doi:10.1124/dmd.105. 005579, dmd.105.005579 [pii]
74. Pichard L, Fabre I, Daujat M, Domergue J, Joyeux H, Maurel P (1992) Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes. Mol Pharmacol 41(6):1047-1055
75. Wilkinson G, Shand D (1975) A physiological approach to hepatic drag clearance. Clin Pharmacol Ther 18:377-390
76. Houston J (1982) Drug metabolite kinetics. Pharmacol Ther 15:521-552
77. Tozer T (1981) Concepts basic to pharmacokinetics. Pharmac Ther 12:109-131
78. Polasek TM, Miners JO (2007) In vitro approaches to investigate mechanism-based inactivation of CYP enzymes. Expert Opin Drug Metab Toxicol 3(3):321-329. doi:10. 1517/17425255.3.3.321
79. Quinney SK, Malireddy SR, Vuppalanchi R, Hamman MA, Chalasani N, Gorski JC, Hall SD (2012) Rate of onset of inhibition of gutwall and hepatic CYP3A by clarithromycin. Eur J Clin Pharmacol. doi:10.1007/s00228-012-1339-x
80. Quinney SK, Zhang X, Lucksiri A, Gorski JC, Li L, Hall SD (2010) Physiologically based pharmacokinetic model of mechanism-based inhibition of CYP3A by clarithromycin. Drug Metab Dispos 38(2):241-248. doi:10.1124/dmd.109. 028746, dmd.109.028746 [pii]
81. Greenblatt DJ, von Moltke LL, Harmatz JS, Chen G, Weemhoff JL, Jen C, Kelley CJ, LeDuc BW, Zinny MA (2003) Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice. Clin Pharmacol Ther 74(2):121-129, 10.1016/S0009-9236(03)00118-8S0009923603001188 [pii]
82. Rowland Yeo K, Walsky RL, Jamei M, Rostami-Hodjegan A, Tucker GT (2011) Prediction of time-dependent CYP3A4 drug-drug interactions by physiologically based pharmacokinetic modelling: Impact of inactivation parameters and enzyme turnover. Eur J Pharm Sci 43(3):160-173. doi:10.1016/j.ejps.2011.04.008, S0928-0987(11)00103-5 [pii]
83. Ogilvie BW, Zhang D, Li W, Rodrigues AD, Gipson AE, Holsapple J, Toren P, Parkinson A (2006) Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: Implications for drugdrug interactions. Drug Metab Dispos 34 (1):191-197. doi:10.1124/dmd.105. 007633, dmd.105.007633 [pii]
84. Einolf HJ (2007) Comparison of different approaches to predict metabolic drug-drug interactions. Xenobiotica 37 (10-11):1257-1294. doi:10.1080/ 00498250701620700, 783595499 [pii]
85. Polasek TM, Miners JO (2006) Quantitative prediction of macrolide drug-drug interaction potential from in vitro studies using testosterone as the human cytochrome P4503A substrate. Eur J Clin Pharmacol 62(3):203-208. doi:10.1007/s00228-005-0091-x
86. Wang YH, Jones DR, Hall SD (2004) Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos 32(2):259-266. doi:10. 1124/dmd.32.2.25932/2/259 [pii]
87. Mao J, Mohutsky MA, Harrelson JP, Wrighton SA, Hall SD (2011) Prediction of CYP3A-mediated drug-drug interactions using human hepatocytes suspended in human plasma. Drug Metab Dispos 39 (4):591-602. doi:10.1124/dmd.110. 036400, dmd.110.036400 [pii]
88. Galetin A, Hinton LK, Burt H, Obach RS, Houston JB (2007) Maximal inhibition of intestinal first-pass metabolism as a pragmatic indicator of intestinal contribution to the drug-drug interactions for CYP3A4 cleared drugs. Curr Drug Metab 8(7):685-693
89. Takanaga H, Ohnishi A, Matsuo H, Murakami H, Sata H, Kuroda K, Urae A, Higuchi S, Sawada Y (2000) Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model. Br J Clin Pharmacol 49(1):49-58
90. Venkatakrishnan K, 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(6):845-852
91. Honkalammi J, Niemi M, Neuvonen PJ, Backman JT (2011) Dose-dependent interaction between gemfibrozil and repaglinide in humans: Strong inhibition of CYP2C8 with subtherapeutic gemfibrozil doses. Drug Metab Dispos 39(10):1977-1986. doi:10. 1124/dmd.111.040931, dmd.111.040931 [pii]
92. Kudo T, Hisaka A, Sugiyama Y, Ito K (2012) Analysis of the repaglinide concentration increase produced by gemfibrozil and itraconazole based on the inhibition of the hepatic uptake transporter and metabolic enzymes. Drug Metab Dispos. doi:dmd.112.049460 [pii]10.1124/dmd.112.049460
93. Kenny JR, Mukadam S, Zhang C, Tay S, Collins C, Galetin A, Khojasteh SC (2012) Drug-drug interaction potential of marketed oncology drugs: In vitro assessment of timedependent cytochrome P450 inhibition, reactive metabolite formation and drug-drug interaction prediction. Pharm Res 29 (7):1960-1976. doi:10.1007/s11095-012-0724-6
94. Zhao P, Kunze KL, Lee CA (2005) Evaluation of time-dependent inactivation of CYP3A in cryopreserved human hepatocytes. Drug Metab Dispos 33(6):853-861
95. McGinnity DF, Berry AJ, Kenny JR, Grime K, Riley RJ (2006) Evaluation of timedependent cytochrome P450 inhibition using cultured human hepatocytes. Drug Metab Dispos 34(8):1291-1300
96. Lu C, Berg C, Prakash SR, Lee FW, Balani SK (2008) Prediction of pharmacokinetic drugdrug interactions using human hepatocyte suspension in plasma and cytochrome P450 phenotypic data. III. In vitro-in vivo correlation with fluconazole. Drug Metab Dispos 36 (7):1261-1266. doi:10.1124/dmd.107. 019000, dmd.107.019000 [pii]
97. Lu C, Hatsis P, Berg C, Lee FW, Balani SK (2008) Prediction of pharmacokinetic drugdrug interactions using human hepatocyte suspension in plasma and cytochrome P450 phenotypic data. II. In vitro-in vivo correlation with ketoconazole. Drug Metab Dispos 36(7):1255-1260. doi:10.1124/dmd.107. 018796, dmd.107.018796 [pii]
98. Mao J, Mohutsky MA, Harrelson JP, Wrighton SA, Hall SD (2012) Predictions of cytochrome P450-mediated drug-drug interactions using cryopreserved human hepatocytes: Comparison of plasma and protein-free media incubation conditions. Drug Metab Dispos 40(4):706-716. doi:10.1124/dmd. 111.043158, dmd.111.043158 [pii]
99. Lin HL, Kent UM, Hollenberg PF (2002) Mechanism-based inactivation of cytochrome P450 3A4 by 17 alpha-ethynylestradiol: Evidence for heme destruction and covalent binding to protein. J Pharmacol Exp Ther 301(1):160-167
100. Belle DJ, Callaghan JT, Gorski JC, Maya JF, Mousa O, Wrighton SA, Hall SD (2002) The effects of an oral contraceptive containing ethinyloestradiol and norgestrel on CYP3A activity. Br J Clin Pharmacol 53 (1):67-74