In Vitro Approaches to Anticipating Clinical Drug Interactions

Drug-Drug Interactions in Pharmaceutical Development

Volumn , Issue , 2007, Pages 31-74

  Volak, Laurie P ^a   Greenblatt, David J ^a   Von Moltke, Lisa L ^b  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Milennium Pharmaceutical Inc   (United States)

Author keywords

Human liver microsomes (HLMs); Metabolic pathways; Parallel tube model

Indexed keywords

EID: 84889396630     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470187920.ch2     Document Type: Chapter

References (158)

1. Ameer B, Greenblatt DJ. Acetaminophen. Ann Intern Med 1977;87:202-209.
2. Attar M, Dong D, Ling KH, Tang-Liu DD. Cytochrome P450 2C8 and flavincontaining monooxygenases are involved in the metabolism of tazarotenic acid in humans. Drug Metab Dispos 2003;31:476-481.
3. Bass L, Keiding S. Physiologically based models and strategic experiments in hepatic pharmacology. Biochem Pharmacol 1988;37:1425-1431.
4. Beedham C, Miceli JJ, Obach RS. Ziprasidone metabolism, aldehyde oxidase, and clinical implications. J Clin Psychopharmacol 2003;23:229-232.
5. Bertelsen KM, Venkatakrishnan K, von Moltke LL, Obach RS, Greenblatt DJ. Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine:comparison with fluoxetine and quinidine. Drug Metab Dispos 2003;31:289-293.
6. Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet 1997;32:210-258.
7. Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, Kumar G, McLeod J, Obach SR, Roberts S, Roe A, Shah A, Snikeris F, Sullivan JT, Tweedie D, Vega JM, Walsh J, Wrighton SA. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharmacol 2003;43:443-469.
8. Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, Danley DE, Hoth LR, Griffor MC, Kamath AV, Rosner MH, Chrunyk BA, Perregaux DE, Gabel CA, Geoghegan KF, Pandit J. Identification, characterization, and crystal structure of the Omega class glutathione transferases. J Biol Chem 2000;275:24798-24806.
9. Bourrié M, Meunier V, Berger Y, Fabre G. Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J Pharmacol Exp Ther 1996;277:321-332.
10. Busby WF, Ackermann JM, Crespi CL. Effect of methanol, ethanol, dimethyl sulfoxide, and acetonitrile on in vitro activities of cDNA-expressed human cytochromes P-450. Drug Metab Dispos 1999;27:246-249.
11. Carlile DJ, Hakooz N, Bayliss MK, Houston JB. Microsomal prediction of in vivo clearance of CYP2C9 substrates in humans. Br J Clin Pharmacol 1999;47:625-635.
12. Cashman JR. In vitro metabolism: FMO and related oxygenations. In: Wolfe TR, editor. Handbook of drug metabolism. Ann Arbor: Marcel Dekker Inc.; 1999. p 477-506.
13. Cashman JR, Zhang J. Human flavin-containing monooxygenases. Annu Rev Pharmacol Toxicol 2006;46:65-100.
14. Charasson V, Bellott R, Meynard D, Longy M, Gorry P, Robert J. Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38. Clin Pharmacol Ther 2004;76:528-535.
15. Chatterjee B, Echchgadda I, Song CS. Vitamin D receptor regulation of the steroid/bile acid sulfotransferase SULT2 A1. Methods Enzymol 2005;400:165-191.
16. Chauret N, Gauthier A, Nicoll-Griffith DA. Effect of common organic solvents on in vitro cytochrome P450-mediated metabolic activities in human liver microsomes. Drug Metab Dispos 1998;26:1-4.
17. Chung WG, Park CS, Roh HK, Lee WK, Cha YN. Oxidation of ranitidine by isozymes of flavin-containing monooxygenase and cytochrome P450. Japan J Pharmacol 2000;84:213-220.
18. Cohen LH, Remley MJ, Raunig D, Vaz AD. In vitro drug interactions of cytochrome P450:an evaluation of fluorogenic to conventional substrates. Drug Metab Dispos 2003;31:1005-1015.
19. Cotreau-Bibbo MM, von Moltke LL, Greenblatt DJ. Influence of polyethylene glycol and acetone on the in vitro biotransformation of tamoxifen and alprazolam by human liver microsomes. J Pharm Sci 1996;85:1180-1185.
20. Coughtrie MW. Sulfation through the looking glass-recent advances in sulfotransferase research for the curious. Pharmacogenom J 2002;2:297-308.
21. Court MH, Duan SX, Guillemette C, Journault K, Krishnaswamy S, von Moltke LL, Greenblatt DJ. Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1 A9. Drug Metab Dispos 2002;30:1257-1265.
22. Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO, Mackenzie PI. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. J Pharmacol Exp Ther 2001;299:998-1006.
23. Court MH, Greenblatt DJ. Biochemical basis for deficient paracetamol glucuronidation in cats: an interspecies comparison of enzyme constraint in liver microsomes. J Pharm Pharmacol 1997a;49:446-449.
24. Court MH, Greenblatt DJ. Molecular basis for deficient acetaminophen glucuronidation in cats. Biochem Pharmacol 1997b;53:1041-1047.
25. Court MH, Hao Q, Krishnaswamy S, Bekaii-Saab T, Al-Rohaimi A, von Moltke LL, Greenblatt DJ. UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics:UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. J Pharmacol Exp Ther 2004;310:656-665.
26. Court MH, Krishnaswamy S, Hao Q, Duan SX, Patten CJ, von Moltke LL, Greenblatt DJ. Evaluation of 30-azido-30-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism. Drug Metab Dispos 2003;31:1125-1133.
27. Culm-Merdek KE, von Moltke LL, Gan L, Horan KA, Reynolds R, Harmatz JS, Court MH, Greenblatt DJ. Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: comparison with ritonavir. Clin Pharm Ther 2006;79:243-254.
28. Culm-Merdek KE, von Moltke LL, Harmatz JS, Greenblatt DJ. Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics. Br J Clin Pharmacol 2005;60:486-493.
29. Davit B, Reynolds K, Yuan R, Ajayi F, Conner D, Fadiran E, Gillespie B, Sahajwalla C, Huang SM, Lesko LJ. FDA evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug-drug interactions: impact on labeling. J Clin Pharmacol 1999;39:899-910.
30. Desta Z, Soukhova NV, Flockhart DA. Inhibition of cytochrome P450 (CYP450) isoforms by isoniazid: potent inhibition of CYP2C19 and CYP3A. Antimicrob Agents Chemother 2001;45:382-392.
31. Easterbrook J, Lu C, Sakai Y, Li AP. Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes. Drug Metab Dispos 2001;29:141-144.
32. Egnell AC, Houston B, Boyer S. In vivo CYP3A4 heteroactivation is a possiblemechanism for the drug interacton between felbamate and carbamazepine. J Pharmacol Exp Ther 2003;305:1251-1262.
33. Ekins S, Ring BJ, Binkley SN, Hall SD, Wrighton SA. Autoactivation and activation of the cytochrome P450s. Int J Clin Pharmacol Ther 1998;36:642-651.
34. Ernest CS, Hall SD, Jones DR. Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther 2005;312:583-591.
35. Ferst A. Structure and mechanism in protein science: a guide to enzyme catalysis and protein folding. New York, NY: W.H. Freeman and Company; 2000.
36. Fisher MB, Campanale K, Ackermann BL, van den Branden M, Wrighton SA. In vitro glucuronidation using human liver microsomes and the pore-forming peptide alamethicin. Drug Metab Dispos 2000;28:560-566.
37. Fleming CD, Bencharit S, Edwards CC, Hyatt JL, Tsurkan L, Bai F, Fraga C, Morton CL, Howard-Williams EL, Potter PM, Redinbo MR. Structural insights into drug processing by human carboxylesterase 1. Tamoxifen, mevastatin, and inhibition by benzil. J Mol Biol 2005;352:165-177.
38. Foti RS, Fisher MB. Impact of incubation conditions on bufuralol human clearance predictions: enzyme lability and nonspecific binding. Drug Metab Dispos 2004;32:295-304.
39. Frye R, Bertz R, Granneman GR, Qian J, Lamm J, Dennis S, Valdes J. Effect of ritonavir on the pharmacokinetics and pharmacodynamics of alprazolam, Abstract A-59. Program and abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; Toronto, Canada; 1997.
40. Galetin A, Clarke SE, Houston JB. Multisite kinetic analysis of interactions between prototypical CYP3A4 subgroup substrates: midazolam, testosterone, and nifedipine. Drug Metab Dispos 2003;31:1108-1116.
41. Galetin A, Ito K, Hallifax D and Houston JB. CYP3A4 substrate selection and substitution in the prediction of potential dug-drug interactions. Journal of Pharmacology and Experimental Therapeutics 2005;314:180-190.
42. Geshi E, Kimura T, Yoshimura M, Suzuki H, Koba S, Sakai T, Saito T, Koga A, Muramatsu M, Katagiri T. A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity. Hypertens Res 2005;28:719-725.
43. Giancarlo GM, Venkatakrishnan K, Granda BW, von Moltke LL, Greenblatt DJ. Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro:inhibition by sulfaphenazole, omeprazole and ticlopidine. Eur J Clin Pharmacol 2001;57:31-36.
44. Glatt H, Meinl W. Pharmacogenetics of soluble sulfotransferases (SULTs). Naunyn Schmiedebergs Arch Pharmacol 2004;369:55-68.
45. Glatt H, Boeing H, Engelke CE, Ma L, Kuhlow A, Pabel U, Pomplun D, Teubner W, Meinl W. Human cytosolic sulphotransferases: genetics, characteristics, toxicological aspects. Mutat Res 2001;482:27-40.
46. Gorsky LD, Coon MJ. Effects of conditions for reconstitution with cytochrome b5 on the formation of products in cytochrome P-450-catalyzed reactions. Drug Metab Dispos 1986;14:89-96.
47. Greenblatt DJ, von Moltke LL. Sedative-hypnotic and anxiolytic agents. In: Levy RH, Thummel KE, Trager WF, Hansten PD, Eichelbaum M, editors. Metabolic drug interactions. Philadelphia: Lippincott, Williams and Wilkins; 2000. p 259-270.
48. Greenblatt DJ, von Moltke LL, Harmatz JS, Durol AL, Daily JP, Graf JA, Mertzanis P, Hoffman JL, Shader RI. Differential impairment of triazolam and zolpidem clearance by ritonavir. J Acquir Immune Defic Syndr 2000a;24:129-136.
49. Greenblatt DJ, von Moltke LL, Harmatz JS, Durol AL, Daily JP, Graf JA, Mertzanis P, Hoffman JL, Shader RI. Alprazolam-ritonavir interaction: implications for product labeling. Clin Pharmacol Ther 2000b;67:335-341.
50. Guengerich FP. Reactions and significance of cytochrome P-450 enzymes. J Biol Chem 1991;266:10019-10022.
51. Guillemette C. Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenom J 2003;3:136-158.
52. Hein DW, Doll MA, Fretland AJ, Leff MA, Webb SJ, Xiao GH, Devanaboyina US, Nangju NA, Feng Y. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomarkers Prev 2000;9:29-42.
53. Hickman D, Wang JP, Wang Y, Unadkat JD. Evaluation of the selectivity of in vitro probes and suitability of organic solvents for the measurement of human cytochrome P450 monooxygenase activities. Drug Metab Dispos 1998;26:207-215.
54. Houston JB, Carlile DJ. Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. Drug Metab Rev 1997;29:891-922.
55. Houston JB, Kenworthy KE. In vitro-in vivo scaling of CYP kinetic data not consistent with the classical Michaelis-Menten model. Drug Metab Dispos 2000;28:246-254.
56. Hu M, Krausz K, Chen J, Ge X, Li J, Gelboin HL, Gonzalez FJ. Identification of CYP1A2 as the main isoform for the phase I hydroxylated metabolism of genistein and a prodrug converting enzyme of methylated isoflavones. Drug Metab Dispos 2003;31:924-931.
57. Hutzler JM, Frye RF, Korzekwa KR, Branch RA, Huang SM, Tracy TS. Minimal in vivo activation of CYP2C9-mediated flurbiprofen metabolism by dapsone. Eur J Pharm Sci 2001a;14:47-52.
58. Hutzler JM, Hauer MJ, Tracy TS. Dapsone activation of CYP2C9-mediated metabolism: evidence for activation of multiple substrates and a two-site model. Drug Metab Dispos 2001b;29:1029-1034.
59. Ito K, Brown HS, Houston JB. Database analyses for the prediction of in vivo drug-drug interactions from in vitro data. Br J Clin Pharmacol 2004;57:473-486.
60. Ito K, Houston JB. Prediction of human drug clearance from in vitro and preclinical data using physiologically based and empirical approaches. Pharm Res 2005;22:103-112.
61. Iwatsubo T, Hirota N, Ooie T, Suzuki H, Shimada N, Chiba K, Ishizaki T, Green CE, Tyson CA, Sugiyama Y. Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data. Pharmacol Ther 1997;73:147-171.
62. Johnson DL, Lewis BC, Elliot DJ, Miners JO, Martin LL. Electrochemical characterisation of the human cytochrome P450 CYP2 C9. Biochem Pharmacol 2005;69:1533-1541.
63. Kalvass JC, Tess DA, Giragossian C, Linhares MC, Maurer TS. Influence of microsomal concentration on apparent intrinsic clearance: implications for scaling in vitro data. Drug Metab Dispos 2001;29:1332-1336.
64. Kauffman FC. Sulfonation in pharmacology and toxicology. Drug Metab Rev 2004;36:823-843.
65. Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T. Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol 2000;55:843-852.
66. Kawashima K, Hosoi K, Naruke T, Shiba T, Kitamura M, Watabe T. Aldehyde oxidase-dependent marked species difference in hepatic metabolism of the sedativehypnotic, zaleplon, between monkeys and rats. Drug Metab Dispos 1999;27:422-428.
67. Kedderis GL, Rickert DE. Loss of rat liver microsomal cytochrome P-450 during methimazole metabolism. Role of flavin-containing monooxygenase. Drug Metab Dispos 1985;13:58-61.
68. Kenworthy KE, Bloomer JC, Clarke SE, Houston JB. CYP3A4 drug interactions:correlation of 10 in vitro probe substrates. Br J Clin Pharmacol 1999;48:716-727.
69. Kiang TK, Ensom MH, Chang TK. UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol Ther 2005;106:97-132.
70. Kitz R, Wilson IB. Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J Biol Chem 1962;237:3245-3249.
71. Korzekwa KR, Krishnamachary N, Shou M, Ogai A, Parise RA, Rettie AE, Gonzalez FJ, Tracy TS. Evaluation of atypical cytochrome P450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry 1998;37:4137-4147.
72. Krynetski EY, Schuetz JD, Galpin AJ, Pui CH, Relling MV, Evans WE. A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proc Natl Acad Sci USA 1995;92:949-953.
73. Kusama M, Kubota T, Matsukura Y, Matsuno K, Ogawa S, Kanda Y, Iga T. Influence of glutathione S-transferase A1 polymorphism on the pharmacokinetics of busulfan. Clin Chim Acta 2006;368:93-98.
74. Lasker JM, Huang MT, Conney AH. In vivo activation of zoxazolamine metabolism by flavone. Science 1982;216:1419-1421.
75. Larrey D, Pageaux GP. Genetic predisposition to drug-induced hepatotoxicity. J Hepatol 1997;26 (Suppl 2):12-21.
76. Lewis DF. On the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics: towards the prediction of human p450 substrate specificity and metabolism. Biochem Pharmacol 2000;60:293-306.
77. Lewis DF, Pratt JM. The P450 catalytic cycle and oxygenation mechanism. Drug Metab Rev 1998;30:739-786.
78. Lightning LK, Jones JP, Friedberg T, Pritchard MP, Shou M, Rushmore TH, Trager WF. Mechanism-based inactivation of cytochrome P450 3A4 by L-754,394. Biochemistry 2000;39:4276-4287.
79. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46:3-26.
80. Lin Y, Lu P, Tang C, Mei Q, Sandig G, Rodrigues AD, Rushmore TH, Shou M. Substrate inhibition kinetics for cytochrome P450-catalyzed reactions. Drug Metab Dispos 2001;29:368-374.
81. Lipsky JJ, Shen ML, Naylor S. In vivo inhibition of aldehyde dehydrogenase by disulfiram. Chem Biol Interact 2001;130-132:93-102.
82. Lundstrom K, Tenhunen J, Tilgmann C, Karhunen T, Panula P, Ulmanen I. Cloning, expression and structure of catechol-O-methyltransferase. Biochim Biophys Acta 1995;1251:1-10.
83. Lu P, Lin Y, Rodrigues AD, Rushmore TH, Baillie TA, Shou M. Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin bind to different domains within the active site of cytochrome P450 3 A4. Drug Metab Dispos 2001;29:1473-1479.
84. Mäenpää J, Hall SD, Ring BJ, Strom SC, Wrighton SA. Human cytochrome P450 3A (CYP3A) mediated midazolam metabolism: the effect of assay conditions and regioselective stimulation by alpha-naphthoflavone, terfenadine and testosterone. Pharmacogenetics 1998;8:137-155.
85. Margolis JM, Obach RS. Impact of nonspecific binding to microsomes and phospholipid on the inhibition of cytochrome P4502 D6:implications for relating in vitro inhibition data to in vivo drug interactions. Drug Metab Dispos 2003;31:606-611.
86. Mannervik B, Awasthi YC, Board PG, Hayes JD, Di Ilio C, Ketterer B, Listowsky I, Morgenstern R, Muramatsu M, Pearson WR, et al. Nomenclature for human glutathione transferases. Biochem J 1992;282 (Pt 1):305-306.
87. Mayhew BS, Jones DR, Hall SD. An in vitro model for predicting in vivo inhibition of cytochrome P450 3A4 by metabolic intermediate complex formation. Drug Metab Dispos 2000;28:1031-1037.
88. Meijer J, DePierre JW. Cytosolic epoxide hydrolase. Chem Biol Interact 1988;64:207-249.
89. McLure JA, Miners JO, Birkett DJ. Nonspecific binding of drugs to human liver microsomes. Br J Clin Pharmacol 2000;49:453-461.
90. Meyer UA, Zanger UM. Molecular mechanisms of genetic polymorphisms of drug metabolism. Annu Rev Pharmacol Toxicol 1997;37:269-296.
91. Michaelis M, Menten ML. Die Kinetic der Invertinwirkung. Biochem Z 1913;49:333-369.
92. Miners JO, Knights KM, Houston JB, Mackenzie PI. In vitro-in vivo correlation for drugs and other compounds eliminated by glucuronidation in humans: pitfalls and promises. Biochem Pharmacol 2006;71:1531-1539.
93. Motulsky HJ, Ransnas LA. Fitting curves to data using nonlinear regression: a practical and nonmathematical review. FASEB J 1987;1:365-374.
94. Nagilla R, Frank KA, Jolivette LJ, Ward KW. Investigation of the utility of published in vitro intrinsic clearance data for prediction of in vivo clearance. J Pharmacol Toxicol Methods 2006;53:106-116.
95. Niro R, Byers JP, Fournier RL, Bachmann K. Application of a convective-dispersion model to predict in vivo hepatic clearance from in vitro measurements utilizing cryopreserved human hepatocytes. Curr Drug Metab 2003;4:357-369.
96. Obach RS, Huynh P, Allen MC, Beedham C. Human liver aldehyde oxidase: inhibition by 239 drugs. J Clin Pharmacol 2004;44:7-19.
97. Obach RS, Reed-Hagen AE. Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos 2002;30:831-837.
98. Obach RS, Walsky RL, Venkatakrishnan K, Gaman EA, Houston JB, Tremaine LM. The utility of in vitro cytochrome P450 inhibition data in the prediction of drug-drug interactions. J Pharmacol Exp Ther 2006;316:336-348.
99. Pacifici GM. Inhibition of human liver and duodenum sulfotransferases by drugs and dietary chemicals: a review of the literature. Int J Clin Pharmacol Ther 2004;42:488-495.
100. Patki KC, von Moltke LL, Greenblatt DJ. In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes P450:role of CYP3A4 and CYP3A5. Drug Metab Dispos 2003;31:938-944.
101. Pemble SE, Taylor JB. An evolutionary perspective on glutathione transferases inferred from class-theta glutathione transferase cDNA sequences. Biochem J 1992;287 (Pt 3):957-963.
102. Perloff ES, Duan SX, Skolnik PR, Greenblatt DJ, von Moltke LL. Atazanavir: effects on P-glycoprotein transport and CYP3A metabolism in vitro. Drug Metab Dispos 2005;33:764-770.
103. Polasek TM, Miners JO. Quantitative prediction of macrolide drug-drug interaction potential from in vitro studies using testosterone as the human cytochrome P4503A substrate. Eur J Clin Pharmacol 2006;62:203-208.
104. Quinney SK, Sanghani SP, Davis WI, Hurley TD, Sun Z, Murry DJ, Bosron WF. Hydrolysis of capecitabine to 50-deoxy-5-fluorocytidine by human carboxylesterases and inhibition by loperamide. J Pharmacol Exp Ther 2005;313:1011-1016.
105. Racha JK, Zhao ZS, Olejnik N, Warner N, Chan R, Moore D, Satoh H. Substrate dependent inhibition profiles of fourteen drugs on CYP3A4 activity measured by a high throughput LCMS/MS method with four probe drugs, midazolam, testosterone, nifedipine and terfenadine. Drug Metab Pharmacokinet 2003;18:128-138.
106. Raftogianis RB, Wood TC, Otterness DM, van Loon JA, Weinshilboum RM. Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. Biochem Biophys Res Commun 1997; 239:298-304.
107. Renwick AB, Ball SE, Tredger JM, Price RJ, Walters DG, Kao J, Scatina JA, Lake BG. Inhibition of zaleplon metabolism by cimetidine in the human liver: in vitro studies with subcellular fractions and precision-cut liver slices. Xenobiotica 2002; 32:849-862.
108. Rettie AE, Meier GP, Sadeque AJ. Prochiral sulfides as in vitro probes for multiple forms of the flavin-containing monooxygenase. Chem Biol Interact 1995;96:3-15.
109. Riley RJ, McGinnity DF, Austin RP. A unified model for predicting human hepatic, metabolic clearance from in vitro intrinsic clearance data in hepatocytes and microsomes. Drug Metab Dispos 2005;33:1304-1311.
110. Roberts MS, Rowland M. A dispersion model of hepatic elimination: 1. Formulation of the model and bolus considerations. J Pharmacokinet Biopharm 1986a;14:227-260.
111. Roberts MS, Rowland M. Correlation between in-vitro microsomal enzyme activity and whole organ hepatic elimination kinetics: analysis with a dispersion model. J Pharm Pharmacol 1986b;38:177-181.
112. Rowland M, Benet LZ, Graham GG. Clearance concepts in pharmacokinetics. J Pharmacokinet Biopharm 1973;1:123-136.
113. Runge-Morris M, Kocarek TA. Regulation of sulfotransferases by xenobiotic receptors. Curr Drug Metab 2005;6:299-307.
114. Salsali M, Holt A, Baker GB. Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2 D6. Cell Mol Neurobiol 2004;24:63-76.
115. Sanghani SP, Quinney SK, Fredenburg TB, Davis WI, Murry DJ, Bosron WF. Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, C ES3. Drug Metab Dispos 2004;32:505-511.
116. Satoh T, Hosokawa M. The mammalian carboxylesterases: from molecules to functions. Annu Rev Pharmacol Toxicol 1998;38:257-288.
117. Schenkman JB, Jansson I. The many roles of cytochrome b5. Pharmacol Ther 2003; 97:139-152.
118. Shou M, Dai R, Cui D, Korzekwa KR, Baillie TA, Rushmore TH. A kinetic model for the metabolic interaction of two substrates at the active site of cytochrome P450 3 A4. J Biol Chem 2001a;276:2256-2262.
119. Shou M, Grogan J, Mancewicz JA, Krausz KW, Gonzalez FJ, Gelboin HV, Korzekwa KR. Activation of CYP3 A4:evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. Biochemistry 1994;33:6450-6455.
120. Shou M, Lin Y, Lu P, Tang C, Mei Q, Cui D, Tang W, Ngui JS, Lin CC, Singh R, Wong BK, Yergey JA, Lin JH, Pearson PG, Baillie TA, Rodrigues AD, Rushmore TH. Enzyme kinetics of cytochrome P450-mediated reactions. Curr Drug Metab 2001b;2:17-36.
121. Shou M, Mei Q, Ettore MW Jr.Dai R, Baillie TA, Rushmore TH. Sigmoidal kinetic model for two co-operative substrate-binding sites in a cytochrome P450 3A4 active site: an example of the metabolism of diazepam and its derivatives. Biochem J 1999;340(Pt 3):845-853.
122. Silverman RB. Mechanism-based enzyme inactivators. Methods Enzymol 1995; 249:240-283.
123. Spielberg SP, Gordon GB. Glutathione synthetase-deficient lymphocytes and acetaminophen toxicity. Clin Pharmacol Ther 1981;29:51-55.
124. Song CS, Echchgadda I, Baek BS, Ahn SC, Oh T, Roy AK, Chatterjee B. Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated farnesoid X receptor. J Biol Chem 2001;276:42549-42556.
125. Stone AN, Mackenzie PI, Galetin A, Houston JB, Miners JO. Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human udp-glucuronosyltransferases:evidence for atypical glucuronidation kinetics by UGT2 B7. Drug Metab Dispos 2003;31:1086-1089.
126. Strittmatter CF, Ball EG. A hemochromagen component of liver microsomes. Proc Natl Acad Sci USA 1952;38:19-25.
127. Tanaka E. Update: genetic polymorphism of drug metabolizing enzymes in humans. J Clin Pharm Ther 1999;24:323-329.
128. Tang W, Stearns RA, Kwei GY, Iliff SA, Miller RR, Egan MA, Yu NX, Dean DC, Kumar S, Shou M, Lin JH, Baillie TA. Interaction of diclofenac and quinidine in monkeys: stimulation of diclofenac metabolism. J Pharmacol Exp Ther 1999;291:1068-1074.
129. Tang C, Shou M, Rodrigues AD. Substrate-dependent effect of acetonitrile on human liver microsomal cytochrome P450 2C9 (CYP2C9) activity. Drug Metab Dispos 2000;28:567-572.
130. Thummel KE, Kunze KL, Shen DD. Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction. Adv Drug Deliv Rev 1997;27:99-127.
131. Tran TH, von Moltke LL, Venkatakrishnan K, Granda BW, Gibbs MA, Obach RS, Harmatz JS, Greenblatt DJ. Microsomal protein concentration modifies the apparent inhibitory potency of CYP3A inhibitors. Drug Metab Dispos 2002;30:1441-1445.
132. Tucker GT, Houston JB, Huang SM. Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential-towards a consensus. Br J Clin Pharmacol 2001;52:107-117.
133. Uchaipichat V, Mackenzie PI, Guo XH, Gardner-Stephen D, Galetin A, Houston JB, Miners JO. Human udp-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid. Drug Metab Dispos 2004; 32:413-423.
134. Ueng YF, Hsieh CH, Don MJ. Inhibition of human cytochrome P450 enzymes by the natural hepatotoxin safrole. Food Chem Toxicol 2005;43:707-712.
135. Ueng YF, Kuwabara T, Chun YJ, Guengerich FP. Cooperativity in oxidations catalyzed by cytochrome P450 3A4. Biochemistry 1997;36:370-381.
136. Umeda S, Harakawa N, Yamamoto M, Ueno K. Effect of nonspecific binding to microsomes and metabolic elimination of buprenorphine on the inhibition of cytochrome P4502 D6. Biol Pharm Bull 2005;28:212-216.
137. Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Relative quantities of catalytically active CYP 2C9 and 2C19 in human liver microsomes: application of the relative activity factor approach. J Pharmaceut Sci 1998;87:845-853.
138. Venkatakrishnan K, von Moltke LL, Obach RS, Greenblatt DJ. Microsomal binding of amitriptyline: effect on estimation of enzyme kinetic parameters in vitro. J Pharmacol Exp Ther 2000a;293:343-350.
139. Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Effects of the antifungal agents on oxidative drug metabolism in humans: clinical relevance. Clin Pharmacokinet 2000b;38:111-180.
140. Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Human drug metabolism and the cytochromes P450:application and relevance of in vitro models. J Clin Pharmacol 2001;41:1149-1179.
141. Venkatakrishnan K, von Moltke LL, Obach RS, Greenblatt DJ. Drug metabolism and drug interactions: application and clinical value of in vitro models. Curr Drug Metab 2003;4:423-459.
142. von Moltke LL, Durol ALB, Duan SX, Greenblatt DJ. Potent mechanism-based inhibition of human CYP3A in vitro by amprenavir and ritonavir: comparison with ketoconazole. Eur J Clin Pharmacol 2000;56:259-261.
143. von Moltke LL, Greenblatt DJ, Harmatz JS, Duan SX, Harrel LM, Cotreau-Bibbo MM, Pritchard GA, Wright CE, Shader RI. Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors, and clinical confirmation of a predicted interaction with ketoconazole. J Pharmacol Exp Ther 1996b;276:370-379.
144. von Moltke LL, Greenblatt DJ, Granda BW, Duan SX, Grassi JM, Venkatakrishnan K, Harmatz JS, Shader RI. Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations. Br J Clin Pharmacol 1999;48:89-97.
145. von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Duan SX, Fogelman SM, Daily JP, Harmatz JS, Shader RI. Protease inhibitors as inhibitors of human cytochromes P450:high risk associated with ritonavir. J Clin Pharmacol 1998a; 38:106-111.
146. von Moltke LL, Greenblatt DJ, Schmider J, Duan SX, Wright CE, Harmatz JS, Shader RI. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J Clin Pharmacol 1996a; 36:783-791.
147. von Moltke LL, Greenblatt DJ, Schmider J, Wright CE, Harmatz JS, Shader RI. In vitro approaches to predicting drug interactions in vivo. Biochem Pharmacol 1998b;55:113-122.
148. Voorman RL, Payne NA, Wienkers LC, Hauer MJ, Sanders PE. Interaction of delavirdine with human liver microsomal cytochrome P450:inhibition of CYP2C9, CYP2C19, and CYP2D6. Drug Metab Dispos 2001;29:41-47.
149. Walsky RL, Obach RS, Gaman EA, Gleeson JP, Proctor WR. Selective inhibition of human cytochrome P4502C8 by montelukast. Drug Metab Dispos 2005;33:413-418.
150. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE. Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos 2004;32:1201-1208.
151. Winkler K, Keiding S, Tygstrup N. Clearance as a quantitative measure of liver function. In: Paumgartner P, Presig R, editors. The liver: quantitative aspects of structure and functions. Basel: Karger; 1973. p 144-155.
152. Wynalda MA, Hutzler JM, Koets MD, Podoll T, Wienkers LC. In vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab Dispos 2003; 31:878-887.
153. Yamano K, Yamamoto K, Kotaki H, Sawada Y, Iga T. Quantitative prediction of metabolic inhibition of midazolam by itraconazole and ketoconazole in rats:implication of concentrative uptake of inhibitors into liver. Drug Metab Dispos 1999a;27:395-402.
154. Yamano K, Yamamoto K, Kotaki H, Takedomi S, Matsuo H, Sawada Y, Iga T. Correlation between in vivo and in vitro hepatic uptake of metabolic inhibitors of cytochrome P-450 in rats. Drug Metab Dispos 1999b;27:1225-1231.
155. Yamano K, Yamamoto K, Kotaki H, Takedomi S, Matsuo H, Sawada Y, Iga T. Quantitative prediction of metabolic inhibition of midazolam by erythromycin, diltiazem, and verapamil in rats: implication of concentrative uptake of inhibitors into liver. J Pharmacol Exp Ther 2000;292:1118-1126.
156. Yamazaki H, Ueng YF, Shimada T, Guengerich FP. Roles of divalent metal ions in oxidations catalyzed by recombinant cytochrome P450 3A4 and replacement of NADPH-cytochrome P450 reductase with other flavoproteins, ferredoxin, and oxygen surrogates. Biochemistry 1995;34:8380-8389.
157. Zhang ZY, Wong YN. Enzyme kinetics for clinically relevant CYP inhibition. Curr Drug Metab 2005;6:241-257.
158. Zhang Z, Chen Q, Li Y, Doss GA, Dean BJ, Ngui JS, Silva Elipe M, Kim S, Wu JY, Dininno F, Hammond ML, Stearns RA, Evans DC, Baillie TA, Tang W. In vitro bioactivation of dihydrobenzoxathiin selective estrogen receptor modulators by cytochrome P450 3A4 in human liver microsomes: formation of reactive iminium and quinone type metabolites. Chem Res Toxicol 2005;18:675-685.