Predictive tools for the evaluation of microbial effects on drugs during gastrointestinal passage

Expert Opinion on Drug Metabolism and Toxicology

Volumn 6, Issue 6, 2010, Pages 747-760

  Pieper, Ines A ^a   Bertau, Martin ^a  

^a TU BERGAKADEMIE FREIBERG   (Germany)

Author keywords

Biosimulation; Drug development; Drug metabolism; Gastrointestinal metabolism; In silico models; Saccharomyces cerevisiae

Indexed keywords

ANTIBIOTIC AGENT; FLUOROURACIL; PREBIOTIC AGENT; PROBIOTIC AGENT; SORIVUDINE; DRUG;

ANALYTIC METHOD; BACTERIAL GROWTH; BACTERIAL METABOLISM; COMPUTER MODEL; DRUG ABSORPTION; DRUG DESIGN; DRUG EXCRETION; DRUG METABOLISM; DRUG TRANSFORMATION; ENZYME ACTIVITY; GASTROINTESTINAL TRANSIT; HUMAN; INTESTINE FLORA; NONHUMAN; PREDICTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RELIABILITY; REVIEW; SACCHAROMYCES CEREVISIAE; SIMULATION; XENOBIOTIC METABOLISM; ANIMAL; COMPUTER SIMULATION; DEVICES; DRUG SCREENING; GASTROINTESTINAL TRACT; METABOLISM; MICROBIOLOGY; PROCEDURES; TRENDS;

SACCHAROMYCES CEREVISIAE;

ANIMALS; COMPUTER SIMULATION; DRUG EVALUATION, PRECLINICAL; GASTROINTESTINAL TRACT; HUMANS; PHARMACEUTICAL PREPARATIONS;

EID: 77952480034     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425251003769859     Document Type: Review

References (119)

1. Dickson M, Gagnon J. The cost of new drug discovery and development. Discov Med 2004;22:172-79
2. Adams C, Brantner V. Estimating the cost of new drug development: is it really $802 million? Health Aff 2006;25:420-28
3. Ekins S. Predicting undesirable drug interactions with promiscuous proteins in silico. Drug Discov Today 2004;9:276-85
4. Lennernaes H. Modeling gastrointestinal drug absorption requires more in vivo biopharmaceutical data: experience from in vivo dissolution and permeability studies in humans. Curr Drug Metab 2007;8:645-57
5. Thelen K, Dressman JB. Cytochrome P450-mediated metabolism in the human gut wall. J Pharm Pharmacol 2009;61:541-58
6. Kerr KG. The gastrointestinal microflora: Friends or Foes? J Nutr Env Med 1991;2:39-44
7. Cha C-J, Doerge DR, Cerniglia CE. Biotransformation of malachite green by the fungus Cunnighamella elegans. Appl Env Microbiol 2001;67:4358-60
8. Chatterjee P, Kouzi SA, Pezzuto JM, et al. Biotransformation of the antimelanoma agent betulinic acid by Bacillus megaterium ATCC 13368. Appl Env Microbiol 2000;66:3850-55
9. Zhang D, Freeman JP, Sutherland JB, et al. Biotransformation of chlorpromazine and methdilazine by Cunninghamella elegans. Appl Env Microbiol 1996;62:798-03
10. Griffiths DA, Best DJ, Jezequel SG. The screening of selected microorganisms for use as models of mammalian drug metabolism. Appl Microbiol Biotechnol 1991;35:373-81
11. Randez-Gil F, Aguilera J, Codon A, et al. Baker's yeast: challenges and future prospects. In: de Winde JH editor, Topics in current genetics Vol. 2, Functional genetics of industrial Yeasts. Springer-Verlag: Heidelberg, 2003. p. 57-97
12. De Souza Pereira R The use of baker's yeast in the generation of asymmetric centers to produce chrial drugs and other compounds. Crit Rev Biotechnol 1998;18:25-64
13. Sugano K. Introduction to computational oral absorption simulation. Expert Opin Drug Metab Toxicol 2009;5:259-93
14. Chang C, Swaan PW. Computational approaches to modeling drug transporters. Eur J Pharm Sci 2006;27:411-24
15. Leahy DE. Progress in simulation modelling for pharmacokinetics. Curr Top Med Chem 2003;3:1257-68
16. Bugrim A, Nikolskaya T, Nikolsky Y. Early prediction of drug metabolism and toxicity: systems biology approach and modelling. Drug Discov Today 2004;9:127-35
17. Bertau M, Brusch l, Kummer U. Biosimulation of drug metabolism. In: Bertau M, Mosekilde E, Westerhoff HV, editors. Biosimulation in drug development. Wiley-VCH Verlag GmbH & C. KgaA, Weinheim, 2008 • An overview of different biosimulation approaches in drug development.
18. Jolivette LJ, Ekins S. Methods for predicting human drug metabolism. Adv Clin Chem 2007;43:131-76
19. Ekins S, Ring BJ, Grace J, et al. Present and future in vitro approaches for drug metabolism. J Pharmacol Toxicol Methods 2000;44:313-24
20. Riley RJ, McGinnity DF, Austin RP. A unified model for predicting human hepatic, metabolic clearance from in vitro intrinsic data in hepatocytes and microsomes. Drug Metab Dispos 2005;33:1304-11
21. Cross DM, Bayliss MK. A commentary on the use of hepatocytes in drug metabolism studies during drug discovery and development1. Drug Metab Rev 2000;32:219-40
22. Wolf G. Gut microbiota: a factor in energy regulation. Nutr Rev 2006;64:47-50
23. Isolauri E, Kalliomaki M, Laitinen K, et al. Modulation of the matring gut barrier and microbiota: a novel target in allergic disease. Curr Pharm Des 2008;14:1368-75
24. Macfarlane S, Macfarlane GT. Bacterial diversity in the human gut. Adv Appl Microbiol 2004;54:261-89
25. O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Reports 2006;7:688-93
26. Cummings JH, Macfarlane GT. Role of the intestinal bacteria in nutrient metabolism. Clin Nutr 1997;16:3-11 • An overview of the nutrient metabolism of GI microbiota.
27. Carriere V, Chambaz J, Rousset M. Intestinal responses to xenbiotics. Toxicol in Vitro 2001;15:373-78
28. Hooper LV, Bry L, Falk PG, et al. Host-microbial symbiosis in the mammalian intestine: exploring an internal ecosystem. BioEssays 1998;20:336-43
29. Sousa T, Paterson R, Moore V, et al. The gastrointestinal microbiota as a site for the biotransformation on drugs. Int J Pharm 2008;363:1-25
30. Macfarlane S, Macfarlane GT, Cummings JH. Review article: prebiotics in the gastrointestinal tract. Aliment Pharmacol Ther 2006;24:701-14
31. Young VB, Schmidt TM. Antibiotic-associated diarrhea accompanied by large-scale alterations in the composition of the faecal microbiota. J Clin microbiol 2004;42:1203-06
32. Bohn M, Leppchen K, Katzberg M, et al. Effects of caffeine on stereoselectivities of high cell density biotransformations of cyclic β-keto esters with Saccharomyces cerevisiae. Org Biomol Chem 2007;5:3456-63
33. Bailey MT, Engler H, Sheridan JF. Stress induces the translocation of cutaneous and gastrointestinal microflora to secondary lymphoid organs of C57BL/6 mice. J Neuroimmunology 2006;171:29-37
34. Hopkins MJ, Sharp R, Macfarlane GT. Variation in human intestinal microbiota with age. Digest Liver Dis 2002;34:12-8
35. Whitehead WE, Engel BT, Schuster MM. Irritable Bowel Syndrome physiologiacal and psychological differences between diarrhea-predominant and constipation-predominant patients. Digest Dis Sci 1980;25:404-13
36. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-89
37. Subramanian S, Campbell BJ, Rhodes JM. Bacteria in the pathogenesis of inflammatory bowel disease. Curr Opin Infect Dis 2006;19:475-84
38. Yadav H, Jain S, Sinha PR. Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats. Nutr 2007;23:62-8
39. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008;57:1470-81
40. O'Mahony L, Freeney M, O'Halloran S, et al. Probiotic impact on microbial flora, inflammation and tumor development in IL-10 knock-out mice. Aliment Pharmacol Ther 2001;15:1219-25
41. Jia W, Li H, Zhao L, et al. Gut microbiota: a potential new territory for drug targeting. Nat Rev Drug Discovery 2008;7:123-29 • An article covering the role of GI microbiota in different diseases and as drug target.
42. Shanahan F, Kiely B. The gut microbiota and disease-an inner repository for drug discovery. Drug Discov Today Ther Strateg 2007;4:195-00
43. Isolauri E, Kalliomaki M, Laitinen K, Salminen. Modulation of the maturing gut Barrier and Micobiota: a Novel Target in Allergic Disease. Curr Pharm Des 2008;14:1368-75
44. Walker WA, Duffy LC. Diet and bacterial colonization: Role of probiotics and prebiotics. J Nutr Biochem 1998;9:668-75
45. Kaur IP, Chopra K, Saini A. Probiotics: potential pharmaceutical applications. Eur J Pharm Sci 2002;15:1-9
46. Allen SJ, Okoko B, Martinez E, et al. Probiotics for treating infectious diarrhoea. Cochrane database Syst Rev 2004; 2: CD003048
47. He T, Priebe MG, Zhong Y, et al. Effects of yogurt and bifidobacteria supplementation on the colonic microbiota in lactose-intolerant subjects. J Appl Microbiol 2008;104:595-04
48. Tuohy KM, Rouzaud GCM, Brück WM, et al. Modulation of the human gut microflora towards improved health using prebiotics - assessment of efficacy. Curr Pharm Des 2005;11:75-90
49. Gibson GR, McCartney AL, Rastall RA. Prebiotic and resistance to gastrointestinal infections. Br J Nutr 2006;93:31-4
50. Jeong S-H, Song Y-K, Cho J-H. Risk assessment of ciprofloxacin, flavomycin, olaquindox and colistin sulfate based on microbiological impact on human gut biota. Regulat Toxicol Pharmacol 2009;53:209-16
51. Wikoff WR, Anfora AT, Liu J, et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 2009;106:3698-03
52. Schulz K, Bertau M, Schlenz K, et al. Headspace solid-phase microextraction-gas chromatography-mass spectrometry determination of the characteristic flavourings menthone, isomenthone, neomenthol and menthol in serum samples with and without enzymatic cleavage to validate post-offence alcohol drinking claims. Anal Chim Acta 2009;646:128-40
53. Montalto M, d'Onofrio F, Gallo A, et al. Intestinal microbiota and its function. Dig Liver Dis 2009;3:30-4
54. Pitcher MCL, Cummings JH. Hydrogen suliphide: a bactirial toxin in ulcerative colitis? Gut 1996;39:1-4
55. Diakidou A, Vertzoni M, Goumas K, et al. Characterization of the contents of ascending colon to which drugs are exposed after oral administration to healthy adults. Pharm Res 2009;26:2141-51
56. Okuda H, Ogura K, Kato A, et al. A possible mechanism of eighteen patient deaths caused by interactions of sorivudine, a new antiviral drug, with oral 5-fluorouracil prodrugs. J Pharmacol Exp Ther 1998;287:791-99
57. Davis SS. Formulation strategies for absorption windows. Drug Discovery Today 2005;10:249-57
58. Schrör K. Acetylsalicylic acid. Wiley-Blackwell: Weinheim; 2009. p. 36-39
59. Deloménie C, Fouix S, Longuemaux S, et al. Identification and functional characterisation of arylamine n-acetyltransferases in eubacteria: evidence for highly selective acetylation of 5-aminosalicylic acid. J Bacteriol 2001;183:3417-27
60. Holt R. The bacterial degradation of chloramphenicol. Lancet 1967;1:1259
61. Rafii F, Hotchkiss C, Heinze TM, et al. Metabolism of daidzein by intestinal bacteria from rhesus monkeys (macaca mulatta). Comparat Med 2004;54:165-69
62. Vermes A, Kuijper EJ, Guchelaar HJ, et al. An in vitro study on the active conversion of flucytosine to fluorouracil by microorganisms in the human intestinal microflora. Chemotherapy 2003;49:17-23
63. Goldin BR, Peppercorn MA, Goldmann P. Contribution of host and intestinal microflora in the metabolism of L-dopa by the rat. J Pharmcol Exp Ther 1973;186:160
64. Shu YZ, Kingstone DGI, Van Tassell RL, et al. Metabolism of levamisole, an anti-colon cancer drug by human intestinal bacteria. Xenobiotica 1991;21:737-50
65. Takeno S, Sakai T. The role of the gut flora metabolism in nitrazepam-induced teratogenicity in rats. Eur J Pharmacol 1990;183:2439-40
66. Rafii F, Sutherland JB, Hansen EB, et al. Reduction of nitrazepam by clostridium leptum, a nitroreductase-production bacterium isolated from the human intestinal tract. Clin Infect Dis 1997;25:121-22
67. Gordon HA, Pesti L. The gnotobiotic animal as a tool in the study of host microbial relationships. Microbiol Mol Biol Rev 1971;35:390-29
68. Ilett KF, Tee LBG, Reeves PT, et al. Metabolism of drugs and other xenobiotics in the gut lumen and wall. Pharmacol Ther 1990;46:67-93
69. Karali TT. Comparison of the gastrointestinal anatomy, physiology and biochemistry of human and commonly used laboratory animals. Biopharm Drug Dispos 1995;16:351-80
70. Renwick AG. First-pass metabolism within the lumen of the gastrointestinal tract. In: Gorge CF, Shand G, Renwick AG, editors. Clinical pharmacology and therapeutics, presystemetic drug elimination. Vol. 1. Butterworth Scientific: London; 1982. p. 3-28
71. Edwards CA, Parrett AM. Colonic fermentation- in vitro and in vivo approaches to measurement. Sciences des Aliments 1999;19:291-00
72. Rowland I, Mallett A, Bearne C, et al. Enzyme activities of the hindgut microflora of laboratory animals and man. Xenobiotica 1986;16:519-23
73. Drasar BS, Hill MJ, William REO. The significance of the gut flora in safety testing of food additives. In: Roe FJC, editor. Metabolic aspects of food safety. Academic: New York; 1970
74. Savage DC. Microbial ecology of the gastrointestinal tract. Ann Rev Microbiol 1977;37:107-33
75. Dumas ME, Barton RH, Toye A, et al. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc Natl Acad Sci USA 2006;103:12511-16
76. Richmond J. The 3Rs-Past, present and future. Scand J Lab Anim Sci 2000;2:84-92
77. Gibson GR, Fuller R. Aspects of in vitro and in vivo research approaches directed toward indentifying probiotics and prebiotics for human use. J Nutr 2000;130:391-95
78. Aura A, Oikarinen S, Mutanen M. Suitability of batch in vitro fermentation model using human faecal microbiota for prediction of conversion of flaxseed lignans to enterolactone with reference to an in vivo rat model. Eur J Nutr 2006;45:45-51
79. Molly K, Vande Woestyne M, Verstraete W. Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem. Appl Microbiol Biotechnol 1993;39:254-58
80. Minekus M, Havenaar R. Reactor system. EP0642382; 1998
81. De Boever P, Deplancke B, Verstraete W. Fermentation by gut microbiota cultured in a simulator of the human intestinal microbial ecosystem is improved by supplementing a soygerm powder. J Nutr 2000;130:2599-06
82. Yoo JY, Chen XD. GIT physicochemical modeling-a critical review. Int J Food Eng 2006; 2 • Reviews different in vitro test systems, applied to GI microbiota metabolism.
83. Kontula P, Jaskari J, Nollet l, et al. The colonization of a simulator of the human intestinal microbial ecosystem by a probiotic strain fed on a fermented oat bran product: effects on the gastrointestinal microbiota. Appl Microbiol Biotechnol 1998;50:246-52
84. Alander M, De Smet I, Nollet L, et al. The effect of probiotic strains on the microbiota of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Int J Food Microbiol 1999;46:71-9
85. van de Wiele T, Boon N, Possemiers S, et al. Prebiotic effects of chicory inulin in the simulator of the human intestinal microbial ecosystem. FEMS Microbiol Ecol 2004;51:143-53
86. Possemiers S, Bolca S, Grootaert C, et al. The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine. J Nutr 2006;136:1862-67
87. Schacht E, Gevaert A, Kenawy ER, et al. Polymers for colon specific drug delivery. J Controlled Release 1996;39:327-38
88. Possemiers S, Verthe K, Uyttendaele S, et al. PCR-DGGE-based quantification of stability of the microbial community in a simulator of the human intestinal microbial ecosystem. FEMS Microbiol Ecol 2004;49:495-07
89. Blanquet S, Meunier JP, Minekus M, et al. Recombinant Saccharomyces cerevisiae expressing a P450 in artificial digestive systems: a model for biodetoxication in the human digestive environment. Appl Env Microbiol 2003;69:2884-92
90. Havenaar R, Minekus M. Simulated assimilation. Dairy Ind Int 1996;61:17-3
91. Avantaggiato G, Havenaar R, Visconti A. Assessing the zearalenone binding activity of adsorbent materials during passage through a dynamic gastrointestinal model. Food Chemical Tox 2003;41:1283-90
92. Marteau P, Minekus M, Havenaar R, et al. Survival of lactic acid bacteria in a dynamic model of the stomach and small intestine: validation and the effects of bile. J Dairy Sci 1997;80:1031-37
93. van den Berg R, Havenaar R, Bast A. Bioavailability of ferulic acid is determined by its bioaccessibility. J Cerael Sci 2009;49:296-00
94. ™for the prediction of in vivo performance. Ind Pharm 2006;12:9-12
95. Blanque S, Zeijdner E, Beyssac E, et al. A dynamic artificial gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions. Pharm Res 2004;21:585-91
96. Verwei M, Freidig AP, Havenaar R, et al. Predicted serum folate concentrations based on in vitro studies and kinetic modeling are consistent with measured folate concentrations in humans. J Nutr 2006;136:3074-78
97. Yap CW, Xue Y, Chen YZ. Application of support vector machines to in silico prediction of cytochrome P450 enzyme substrates and inhibitors. Curr Top Med Chem 2006;6:1593-07
98. Mosekilde E, Sosnovtseva OV, Holstein-Rathlou N-H. Mechanism-based modelling of complex biomedical systems. Basic Clin Pharmacol Toxicol 2005;96:212-24
99. Oláh J, Orosz F, Puskás LG, et al. triosephosphate isomerase deficiency: consequences of an inherited mutation at mRNA, protein and metabolic level. Biochem J 2005;392:675-83
100. Chang C, Swaan PW. Computational approaches to modelling drug transporters. Pharm Sci 2006;27:411-24
101. Sugano K. Introduction to computational oral absorption simulation. Expert Opin Drug Metab Toxicol 2009;5:259-93
102. Kapetanovic IM. Computer-aided drug discovery and development (CADDD): in silico-chemico-biological approach. Chemico-biological Interaction 2008;171:165-76
103. Fox T, Kriegl J. Machine learning techniques for in silico modelling of drug metabolism. Curr Top Med Chem 2006;6:1579-91
104. Jones MH, Gardner IB, Watson KJ. Modelling and PBPK simulation in drug discovery. Am Assoc Pharm Scientists 2009;11:155-65
105. Andersen R, Jørgensen FS, Olsen L, et al. Development of a QSAR model for binding of tripeptides and tropeptidomimetics to the human intestinal di-/tripeptide transporter hPEPT1. Pharm Res 2006;23:483-92
106. Li H, Sun J, Fan X, et al. Considerations and recent advances in QSAR models for cytochrome P450 -mediated drug metabolism prediction. J Comput Aided Mol Des 2008;22:843-55
107. Brusch L, Cuniberti G, Bertau M. Model evaluation for glycolytic oscillations in yeast biotransformations of xenobiotics. Biophys Chem 2004;109:413-26 • An article concerning in silico models of Saccharomyces cerevisiae.
108. Pieper I, Wechler K, Katzberg M, et al. Biosimulation of drug metabolism-A yeast based model. Eur J Pharm Sci 2009;36:157-70
109. Giaever G, Chu AM, Ni L, et al. Functional profiling of the Saccharomyces cerevisiae genome. Nature 2002;418:387-91
110. Lee TI, Rinaldi NJ, Robert F, et al. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 2002;298:799-04
111. Cherry JM, Ball C, Weng S, et al. Genetic and physical maps of Saccharomyces cerevisiae. Nature 1997;387:67-73
112. Mewes HW, Albermann K, Bahr M, et al. Overview of the yeast genome. Nature 1997;387:7-8
113. Richard P, Teusink B, Westerhoff HV, et al. Around the growth phase transition S. cerevisiae's make-up favours sustained oscillations of intracellular metabolism. FEBS 1993;318:80-2
114. Rizzi M, Baltes M, Theobald U, et al. In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae. II: mathematical model. Biotech Bioeng 1997;55:592-08
115. Danø S, Sørensen PG, Hynne F. Sustained oscillations in living cells. Nature 1999;402:320-22
116. Wolf J, Heinrich R. Effect of cellular interaction on glycolytic oscillations in yeast: a theoretical investigation. Biochem J 2000;345:321-34
117. Teusink B, Passarge J, Reijenga CA, et al. Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry. Eur J Biochem 2000;267:5313-29
118. Hynne F, Danø S, Sørensen PG. Full-scale model of glycolysis in Saccharomyces cerevisiae. Biophys Chem 2001;94:121-63
119. Reijenga KA, Westerhoff HV, Kholodenko BN, et al. Control analysis of autonomously oscillating biochemical networks. Biophysic J 2002;82:99-08