Biotransformation in vitro: An essential consideration in the quantitative in vitro-to-in vivo extrapolation (QIVIVE) of toxicity data

Toxicology

Volumn 332, Issue , 2015, Pages 8-19

  Wilk Zasadna, Iwona ^a   Bernasconi, Camilla ^a   Pelkonen, Olavi ^b   Coecke, Sandra ^a  

^a JOINT RESEARCH CENTRE   (Italy)

^b UNIVERSITY OF OULU   (Finland)

Author keywords

Biotransformation; In silico; In vitro; Metabolism; PBBK models; QIVIVE

Indexed keywords

ACYLTRANSFERASE; CYTOCHROME P450; EPOXIDE HYDROLASE; GLUCURONOSYLTRANSFERASE; GLUTATHIONE TRANSFERASE; METHYLTRANSFERASE; SULFOTRANSFERASE; THIOPURINE METHYLTRANSFERASE; UNSPECIFIC MONOOXYGENASE; XENOBIOTIC AGENT;

ARTICLE; BIOTRANSFORMATION; CHEMICAL INTERACTION; COMPUTER MODEL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; HAZARD ASSESSMENT; HUMAN; LIQUID CHROMATOGRAPHY; METABOLIC CLEARANCE; METABOLIC STABILITY; METABOLISM; METABOLITE; NONHUMAN; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; QUANTITATIVE IN VITRO IN VIVO EXTRAPOLATION; RISK ASSESSMENT; TANDEM MASS SPECTROMETRY; TARGET ORGAN; TOXICOKINETICS; TOXICOLOGICAL PARAMETERS; ANIMAL; ANIMAL TESTING ALTERNATIVE; BIOLOGICAL MODEL; COMPUTER SIMULATION; IN VITRO STUDY; PROCEDURES; RISK FACTOR; SPECIES DIFFERENCE; SYSTEMS BIOLOGY; TOXICITY TESTING; TOXICOLOGY;

ANIMAL TESTING ALTERNATIVES; ANIMALS; BIOTRANSFORMATION; COMPUTER SIMULATION; HUMANS; IN VITRO TECHNIQUES; MODELS, BIOLOGICAL; RISK ASSESSMENT; RISK FACTORS; SPECIES SPECIFICITY; SYSTEMS BIOLOGY; TOXICITY TESTS; TOXICOLOGY;

EID: 84930081801     PISSN: 0300483X     EISSN: 18793185     Source Type: Journal    
DOI: 10.1016/j.tox.2014.10.006     Document Type: Article

References (132)

1. Abass K., Huusko A., Nieminen P., Myllynen P., Pelkonen O., Vahakangas K., Rautio A. Estimation of health risk by using toxicokinetic modelling: a case study of polychlorinated biphenyl PCB. J. Hazard. Mater. 2013, 261C:1-10.
2. Adler S., Basketter D., Creton S., Pelkonen O., van Benthem J., Zuang V., Andersen K.E., Angers-Loustau A., Aptula A., Bal-Price A., Benfenati E., Bernauer U., Bessems J., Bois F.Y., Boobis A., Brandon E., Bremer S., Broschard T., Casati S., Coecke S., Corvi R., Cronin M., Daston G., Dekant W., Felter S., Grignard E., Gundert-Remy U., Heinonen T., Kimber I., Kleinjans J., Komulainen H., Kreiling K., Kreysa R., Leite J., Loizou S.B., Maxwell G., Mazzatorta G., Munn P., Pfuhler S., Phrakonkham S., Piersma P., Poth A., Prieto A., Repetto P., Rogiers G., Schoeters V., Schwarz G., Serafimova M., Tähti R., Testai H., van Delft E., van Loveren J., Vinken H., Worth M., Zaldivar A. Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010. Arch. Toxicol. 2011, 85:367-485.
3. Alexandre E., Baze A., Parmentier C., Desbans C., Pekthong D., Gerin B., Wack C., Bachellier P., Heyd B., Weber J.-C., Richert L. Plateable cryopreserved human hepatocytes for the assessment of cytochrome P450 inducibility: experimental condition-related variables affecting their response to inducers. Xenobiotica 2012, 42(10):968-979.
4. Anthérieu S., Chesné C., Li R., Camus S., Lahoz A., Picazo L., Turpeinen M., Tolonen A., Uusitalo J., Guguen-Guillouzo C., Guillouzo A. Stable expression, activity, and inducibility of cytochromes P450 in differentiated HepaRG cells. Drug Metab. Dispos. 2010, 38:516-525.
5. Antunes F., Andrade F., Ferreira D., Mørck Nielsen H., Sarmento B. Models to predict intestinal absorption of therapeutic peptides and proteins. Curr. Drug Metab. 2013, 14:4-20.
6. Asha S., Vidyavathi M. Role of human liver microsomes in in vitro metabolism of drugs-a review. Appl. Biochem. Biotechnol. 2010, 160:1699-1722.
7. Baillie T.A. Metabolism and toxicity of drugs. Two decades of progress in industrial drug metabolism. Chem. Res. Toxicol. 2008, 21:129-137.
8. Barbara J.E., Castro-Perez J.M. High-resolution chromatography/time-of-flight MSE with in silico data mining is an information-rich approach to reactive metabolite screening. Rapid Commun. Mass Spectrom. 2011, 25:3029-3040.
9. Barter Z.E., Bayliss M.K., Beaune P.H. Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liver. Curr. Drug Metab. 2007, 8:33-45.
10. Bessems J.G., Loizou G., Krishnan K., Clewell H.J., Bernasconi C., Bois F., Coecke S., Collnot E.-M., Diembeck W., Farcal L.R., Geraets L., Gundert-Remy U., Kramer N., Küsters G., Leite S.B., Pelkonen O.R., Schröder K., Testai E., Wilk-Zasadna I., Zaldívar-Comenges J.-M. PBTK modelling platforms and parameter estimation tools to enable animal-free risk assessment: recommendations from a joint EPAA-EURL ECVAM ADME workshop. Reg. Toxicol. Pharmacol. 2014, 68:119-139.
11. Blaauboer B.J., Boekelheide K., Clewell H.J., Daneshian M., Dingemans M.M.L., Goldberg A.M., Heneweer M., Jaworska J., Kramer N.I., Leist M., Seibert H., Testai E., Vandebriel R.J., Yager J.D., Zurlo J. T4 workshop report: the use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans. Altex 2012, 29:411-415.
12. Blaauboer B.J. The contribution of in vitro toxicity data in hazard and risk assessment: current limitations and future perspectives. Toxicol. Lett. 2008, 180:81-84.
13. Blaauboer B.J. Biokinetic modelling and in vitro-in vivo extrapolation. J. Toxicol. Environ. Health B: Crit. Rev. 2010, 13:242-252.
14. Bonn B., Leandersson C., Fontaine F., Zamora I. Enhanced metabolite identification with MSE and a semi-automated software for structural elucidation. Rapid Commun. Mass Spectrom. 2010, 24:3127-3138.
15. Bouvier d'Yvoire M., Prieto P., Blaauboer B.J., Bois F.Y., Boobis A., Brochot C., Coecke S., Freidig A., Gundert-Remy U., Hartung T., Jacobs M.N., Lavé T., Leahy D.E., Lennernäs H., Loizou G.D., Meek B., Pease C., Rowland M., Spendiff M., Yang J., Zeilmaker M. Physiologically-based kinetic modelling (PBK modelling): meeting the 3Rs agenda. The report and recommendations of ECVAM workshop 63. Altern. Lab. Anim. 2007, 35:661-671.
16. Brown H.S., Griffin M., Houston J.B. Evaluation of cryopreserved human hepatocytes as an alternative in vitro system to microsomes for the prediction of metabolic clearance. Drug Metab. Dispos. 2007, 35:293-301.
17. Cederbaum A.I. Nrf2 and antioxidant defense against CYP2E1 toxicity. Subcell. Biochem. 2013, 67:105-130.
18. Chan E., New L., Yap C., Goh L. Pharmaceutical metabolite profiling using quadrupole/ion mobility spectrometry/time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 2009, 23:384-394.
19. Chang T.K.H. Drug-metabolizing enzymes. Handbook of Drug-Nutrient Interactions 2010, 85-118. Humana Press. J.I. Boullata, V.T. Armenti (Eds.).
20. Chen Y., Liu L., Monshouwer M., Fretland A.J. Determination of time-dependent inactivation of CYP3A4 in cryopreserved human hepatocytes and assessment of human drug-drug interactions. Drug Metab. Dispos. 2011, 39:2085-2092.
21. Chaudhry A.S., Urban T.J., Lamba J.K., Birnbaum A.K., Remmel R.P., Subramanian M., Strom S., You J.H., Kasperaviciute D., Catarino C.B., Radtke R.A., Sisodiya S.M., Goldstein D.B., Schuetz E.G. CYP2C9*1B promoter polymorphisms, in linkage with CYP2C19*2, affect phenytoin autoinduction of clearance and maintenance dose. J. Pharmacol. Exp. Ther. 2010, 332:599-611.
22. Chen Y.F., Tseng C.Y., Wang H.W., Kuo H.C., Yang V.W., Lee O.K. Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol. Hepatology 2012, 55:1193-1203.
23. Coecke S., Ahr H., Blaauboer B.J., Bremer S., Casati S., Castell J., Combes R., Corvi R., Crespi C.L., Cunningham M.L., Elaut G., Eletti B., Freidig A., Gennari A., Ghersi-Egea J.F., Guillouzo A., Hartung T., Hoet P., Ingelman-Sundberg M., Munn S., Janssens W., Ladstetter B., Leahy D., Long A., Meneguz A., Monshouwer M., Morath S., Nagelkerke F., Pelkonen O., Ponti J., Prieto P., Richert L., Sabbioni E., Schaack B., Steiling W., Testai E., Vericat J.A., Worth A. Metabolism: a bottleneck in in vitro toxicological test development. The report and recommendations of ECVAM workshop 54. Altern. Lab. Anim. 2006, 34:49-84.
24. Coecke S., Pelkonen O., Leite S.B., Bernauer U., Bessems J.G.M., Bois F.Y., Gundert-Remy U., Loizou G., Testai E., Zaldivar J.M. Toxicokinetics as a key to the integrated toxicity risk assessment based primarily on non-animal approaches. Toxicol. In Vitro 2013, 27:1570-1577.
25. Cruciani G., Baroni M., Benedetti P., Goracci L., Fortuna C.G. Exposition and reactivity optimization to predict sites of metabolism in chemicals. Drug Discov. Today Technol. 2013, 10:155-165.
26. Crump K.S., Chen C., Louis T.A. The future use of in vitro data in risk assessment to set human exposure standards: challenging problems and familiar solutions. Environ. Health Perspect. 2010, 118:1350-1354.
27. Darnell M., Schreiter T., Zeilinger K., Urbaniak T., Soderdahl T., Rossberg I., Dillner B., Berg A.L., Gerlach J.C., Andersson T.B. Cytochrome P450-dependent metabolism in HepaRG cells cultured in a dynamic three-dimensional bioreactor. Drug Metab. Dispos. 2011, 39:1131-1138.
28. Dekant W. The role of biotransformation and bioactivation in toxicity. Molecular, Clinical and Environmental Toxicology 2009, 1:57-86. Birkhäuser Verlag, Molecular Toxicology.
29. de Graaf I.A., Olinga P., de Jager M.H., Merema M.T., de Kanter R., van de Kerkhof E.G., Groothuis G.M. Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies. Nat Protoc. 2010, 5:1540-1551.
30. Diaz Ochoa J.G., Bucher J., Péry A.R.R., Zaldivar-Comenges J.M., Niklas J., Mauch K. A multi-scale modelling framework for individualized: spatiotemporal prediction of drug effects and toxicological risk. Front. Pharmacol. 2013, 3:1-11.
31. EC EC regulation 1907/2006 of the European parliament and of the council of 18 December 2006 concerning the registration, evaluation, authorisation and restriction of chemicals (REACH). Off. J. Eur. Commun. 2006, L396:1-849.
32. EC EC regulation 1272/2008 of the European parliament and of the council of 18 December 2008 on classification, labelling and packaging of substances and mixtures. Off. J. Eur. Union 2008, L353.
33. EC EC regulation 1223/2009 of the European parliament and of the council of 30 November 2009 on cosmetic products. Off. J. Eur. Union 2009, L342.
34. EC EC directive 2010/63/EU of the European parliament and of the council of 22 September 2010 on the protection of animals used for scientific purposes. Off. J. Eur. Union 2010, L276.
35. Emoto C., Murayama N., Rostami-Hodjegan A., Yamazaki H. Methodologies for investigating drug metabolism at the early drug discovery stage: prediction of hepatic drug clearance and P450 contribution. Curr. Drug Metab. 2010, 11:678-685.
36. Foster J.A., Houston J.B., Hallifax D. Comparison of intrinsic clearances in human liver microsomes and suspended hepatocytes from the same donor livers: clearance-dependent relationship and implications for prediction of in vivo clearance. Xenobiotica 2011, 41:124-136.
37. Foti R.S., Wienkers L.C., Wahlstrom J.L. Application of cytochrome P450 drug interaction screening in drug discovery. Comb. Chem. High Throughput Screen. 2010, 13:145-158.
38. Frederick D.M., Jacinto E.Y., Patel N.N., Rushmore T.H., Tchao R., Harvison P.J. Cytotoxicity of 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT) and analogues in wild type and CYP3A4 stably transfected HepG2 cells. Toxicol. In Vitro 2011, 25:2113-2119.
39. Godoy P., Hewitt N.J., Albrecht U., Andersen M.E., Ansari N., Bhattacharya S., Bode J.G., Bolleyn J., Borner C., Böttger J., Braeuning A., Budinsky R.A., Burkhardt B., Cameron N.R., Camussi G., Cho C.S., Choi Y.J., Craig Rowlands J., Dahmen U., Damm G., Dirsch O., Donato M.T., Dong J., Dooley S., Drasdo D., Eakins R., Ferreira K.S., Fonsato V., Fraczek J., Gebhardt R., Gibson A., Glanemann M., Goldring C.E., Gómez-Lechón M.J., Groothuis G.M., Gustavsson L., Guyot C., Hallifax D., Hammad S., Hayward A., Häussinger D., Hellerbrand C., Hewitt P., Hoehme S., Holzhütter H.G., Houston J.B., Hrach J., Ito K., Jaeschke H., Keitel V., Kelm J.M., Kevin Park B., Kordes C., Kullak-Ublick G.A., LeCluyse E.L., Lu P., Luebke-Wheeler J., Lutz A., Maltman D.J., Matz-Soja M., McMullen P., Merfort I., Messner S., Meyer C., Mwinyi J., Naisbitt D.J., Nussler A.K., Olinga P., Pampaloni F., Pi J., Pluta L., Przyborski S.A., Ramachandran A., Rogiers V., Rowe C., Schelcher C., Schmich K., Schwarz M., Singh B., Stelzer E.H., Stieger B., Stöber R., Sugiyama Y., Tetta C., Thasler W.E., Vanhaecke T., Vinken M., Weiss T.S., Widera A., Woods C.G., Xu J.J., Yarborough K.M., Hengstler J.G. Recent advances in 2D and 3D in vitro systems using primary hepatocytes alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signalling and ADME. Arch. Toxicol. 2013, 87:1315-1530.
40. Greupink R., Schreurs M., Benne M.S., Huisman M.T., Russel F.G. Semi-mechanistic physiologically-based pharmacokinetic modeling of clinical glibenclamide pharmacokinetics and drug-drug-interactions. Eur. J. Pharm. Sci. 2013, 49:819-828.
41. Grimm S.W., Einolf H.J., Hall S.D., He K., Lim H.-K., Ling K.-H.J., Lu C., Nomeir A.A., Seibert E., Skordos K.W., Tonn G.R., Van Horn R., Wang R.W., Wong Y.N., Yang T.J., Obach R.S. 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. 2009, 37:1355-1370.
42. Guengerich F.P. Cytochrome p450 and chemical toxicology. Chem. Res. Toxicol. 2008, 21:70-83.
43. Guillouzo A., Corlu A., Aninat C., Glaise D., Morel F., Guguen-Guillouzo C. The human hepatoma HepaRG cells: a highly differentiated model for studies of liver metabolism and toxicity of xenobiotics. Chem. Biol. Interact. 2007, 168:66-73.
44. Hallifax D., Foster J.A., Houston J.B. Prediction of human metabolic clearance from in vitro systems: retrospective analysis and prospective view. Pharm. Res. 2010, 27:2150-2161.
45. Hein S., Bur M., Schaefer U.F., Lehr C.M. A new pharmaceutical aerosol deposition device on cell cultures (PADDOCC) to evaluate pulmonary drug absorption for metered dose dry powder formulations. Eur. J. Pharm. Biopharm. 2011, 77:132-138.
46. Houston J.B., Rowland-Yeo K., Zanelli U. Evaluation of the novel in vitro systems for hepatic drug clearance and assessment of their predictive utility. Toxicol. In Vitro 2012, 26:1265-1271.
47. + liver stem cells induced by Wnt driven regeneration. Nature 2013, 494:247-250.
48. Jayaraman R., Pilla Reddy V., Pasha M.K., Wang H., Sangthongpitag K., Yeo P., Hu C.Y., Wu X., Xin L., Goh E., New L.S., Ethirajulu K. Preclinical metabolism and disposition of SB939 (pracinostat) an orally active histone deacetylase inhibitor, and prediction of human pharmacokinetics. Drug. Metab. Dispos. 2011, 39:2219-2232.
49. Kanebratt K.P., Andersson T.B. Evaluation of HepaRG cells as an in vitro model for human drug metabolism studies. Drug Metab. Dispos. 2008, 36:1444-1452.
50. Karlgren M., Ingelman-Sundberg M. Tumour-specific expression of CYP2W1: its potential as a drug target in cancer therapy. Exp. Opin. Ther. Targets 2007, 11:61-67.
51. Karlsson F.H., Bouchene S., Hilgendorf C., Dolgos H., Peters S.A. Utility of in vitro systems and preclinical data for the prediction of human intestinal first-pass metabolism during drug discovery and preclinical development. Drug Metab. Dispos. 2013, 41:2033-2046.
52. Ketola R.A., Mauriala T. Mass spectrometric tools for cell and tissue studies. Eur. J. Pharm. Sci. 2012, 46:293-314.
53. Kim T.Y., Kim H.U., Lee S.Y. Metabolite-centric approaches for the discovery of antibacterials using genome-scale metabolic networks. Metab. Eng. 2010, 12:105-111.
54. Kirchmair J., Williamson M.J., Tyzack J.D., Tan L., Bond P.J., Bender A., Glen R.C. Computational prediction of metabolism: sites, products, SAR, P450 enzyme dynamics, and mechanisms. J. Chem. Inf. Mod. 2012, 52:617-648.
55. Kramer N.I. Measuring, Modelling, and Increasing the Free Concentration of Test Chemicals in Cell Assays. PhD Thesis 2010, Utrecht University.
56. Kumar V., Schuck E.L., Pelletier R.D., Farah N., Condon K.B., Ye M., Rowbottom C., King B.M., Zhang Z.Y., Saxton P.L., Wong Y.N. Pharmacokinetic characterization of a natural product-inspired novel MEK1 inhibitor E6201 in preclinical species. Cancer Chemother. Pharmacol. 2011, 69:229-237.
57. Lübberstedt M., Müller-Vieira U., Mayer M., Biemel K.M., Knöspel F., Knobeloch D., Nüssler A.K., Gerlach J.C., Zeilinger K. HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in vitro. J. Pharmacol. Toxicol. Methods 2011, 63:59-68.
58. Lübberstedt M., Müller-Vieira U., Biemel K.M., Darnell M., Hoffmann S.A., Knöspel F., Wönne E.C., Knobeloch D., Nüssler A.K., Gerlach J.C., Andersson T.B., Zeilinger K. Serum-free culture of primary human hepatocytes in a miniaturized hollow-fibre membrane bioreactor for pharmacological in vitro studies. J. Tissue Eng. Regen. Med. 2012, Nov 20. [Epub ahead of print]. 10.1002/term.1652.
59. Lafond M., Bouza B., Eyrichine S., Bonnin E., Crost E.H., Geraert P.A., Giardina T., Ajandouz E.H. An integrative in vitro approach to analyse digestion of wheat polysaccharides and the effect of enzyme supplementation. Br. J. Nutr. 2011, 106:264-273.
60. LeCluyse E.L., Witek R.P., Andersen M.E., Powers M.J. Organotypic liver culture models: Meeting current challenges in toxicity testing. Crit. Rev. Toxicol. 2012, 42:501-548.
61. Lehmann A.D., Daum N., Bur M., Lehr C.M., Gehr P., Rothen-Rutishauser B.M. An in vitro triple cell co-culture model with primary cells mimicking the human alveolar epithelial barrier. Eur. J. Pharm. Biopharm. 2011, 77:398-406.
62. Leite S.B., Wilk-Zasadna I., Zaldivar J.M., Airola E., Reis-Fernandes M.A., Mennecozzi M., Guguen-Guillouzo C., Chesne C., Guillou C., Alves P.M., Coecke S. Three-dimensional HepaRG model as an attractive tool for toxicity testing. Toxicol. Sci. 2012, 130:106-116.
63. Leoni C., Balduzzi M., Buratti F.M., Testai E. The contribution of human small intestine to chlorpyrifos biotransformation. Toxicol. Lett. 2012, 215:42-48.
64. Lerapetritou M.G., Georgopoulos P.G., Roth C.M., Androulakis L.P. Tissue-level modeling of xenobiotic metabolism in liver: An emerging tool for enabling clinical translational research. Clin. Transl. Sci. 2009, 2:228-237.
65. Lerche-Langrand C., Toutain H.J. Precision-cut liver slices: characteristics and use for in vitro pharmaco-toxicology. Toxicology 2000, 153:221-253.
66. Lewis D.F.V., Ito Y. Human CYPs involved in drug metabolism: structures, substrates and binding affinities. Exp. Opin. Drug Metab. Toxicol. 2010, 6:661-674.
67. Ma S., Zhu M. Recent advances in applications of liquid chromatography-tandem mass spectrometry to the analysis of reactive drug metabolites. Chem. Biol. Interact. 2009, 179:25-37.
68. Mandenius C.F., Andersson T.B., Alves P.M., Batzl-Hartmann C., Bjorquist P., Carrondo M.J., Chesne C., Coecke S., Edsbagge J., Fredriksson J.M., Gerlach J.C., Heinzle E., Ingelman-Sundberg M., Johansson I., Kuppers-Munther B., Muller-Vieira U., Noor F., Zeilinger K. Toward preclinical predictive drug testing for metabolism and hepatotoxicity by using in vitro models derived from human embryonic stem cells and human cell lines - a report on the vitrocellomics EU-project. Altern. Lab. Anim. 2011, 39:147-171.
69. Meek M.E., Boobis A.R., Crofton K.M., Heinemeyer G., Van Raaij M., Vickers C. Risk assessment of combined exposure to multiple chemicals: a WHO/IPCS framework. Regul. Toxicol. Pharmacol. 2011, 60:S1-S14.
70. Meyer U.A., Zanger U.M., Schwab M. Omics and drug response. Ann. Rev. Pharmacol. Toxicol. 2013, 53:475-502.
71. Miranda J.P., Leite S.B., Muller-Vieira U., Rodrigues A., Carrondo M.J., Alves P.M. Towards an extended functional hepatocyte in vitro culture. Tissue Eng. C: Meth. 2009, 15:157-167.
72. Mitra P., Venitz J., Yuan Y., Zhang Y., Gerk P. Preclinical disposition (in vitro) of novel μ-opioid receptor selective antagonists. Drug Metab. Dispos. 2011, 39:1589-1596.
73. Moss T., Howes D., Williams F.M. Percutaneous penetration and dermal metabolism of triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether). Food Chem. Toxicol. 2000, 38:361-370.
74. Nordmark A., Andersson A., Baranczewski P., Wanag E., Ståhle L. Assessment of interaction potential of AZD2066 using in vitro metabolism tools, physiologically based pharmacokinetic modelling and in vivo cocktail data. Eur. J. Clin. Pharmacol. 2014, 70:167-178.
75. OECD (2013). Draft Guidance Document 151 in support of OECD Test Guideline 443 on an Extended One Generation Reproductive Toxicity Study. OECD Environmental Health and Safety Publications, Environment Directorate: ENV/JM/MONO(2013)10. 2013; Paris, France:OECD.
76. OECD, Organisation for Economic Cooperation and Development (2008). Test guideline on repeated Dose 28-day oral toxicity study in rodents, Paris.
77. Olinga P., Meijer D.K., Slooff M.J., Groothuis G.M. Liver slices in in vitro pharmacotoxicology with special reference to the use of human liver tissue. Toxicol. In Vitro 1997, 12:77-100.
78. Ong C.E., Pan Y., Mak J.W., Ismail R. In vitro approaches to investigate cytochrome P450 activities: update on current status and their applicability. Exp. Opin. Drug Metab. 2013, 9:1097-1113.
79. Paini A., Punt A., Scholz G., Gremaud E., Spenkelink B., Alink G., Schilter B., van Bladeren P.J., Rietjens I.M. In vivo validation of DNA adduct formation by estragole in rats predicted by physiologically based biodynamic modelling. Mutagenesis 2012, 27:653-663.
80. Park B.K., Boobis A., Clarke S., Goldring C.E., Jones D., Kenna J.G., Lambert C., Laverty H.G., Naisbitt J., Nelson S., Nicoll-Griffith D.A., Obach R.S., Routledge P., Smith D.A., Tweedie D.J., Vermeulen N., Williams D.P., Wilson I.D., Baillie T.A. Managing the challenge of chemically reactive metabolites in drug development. Nat. Rev. Drug Discov. 2011, 10:292.
81. Pelkonen O., Turpeinen M. In vitro-in vivo extrapolation of hepatic clearance: biological tools, scaling factors, model assumptions and correct concentrations. Xenobiotica 2007, 37(10-11):1066-1089. Review.
82. Pelkonen O., Kapitulnik J., Gundert-Remy U., Boobis A.R., Stockis A. Local kinetics and dynamics of xenobiotics. Crit. Rev. Toxicol. 2008, 38:697-720.
83. Pelkonen O., Turpeinen M., Hakkola J., Honkakoski P., Hukkanen J., Raunio H. Inhibition and induction of human cytochrome P450 enzymes-current status. Arch. Toxicol. 2008, 82:667-715.
84. Pelkonen O., Tolonen A., Korjamo T., Turpeinen M., Raunio H. From known knowns to known unknowns: predicting in vivo drug metabolites. Bioanalysis 2009, 1:393-414.
85. Pelkonen O., Tolonen A., Rousu T., Tursas L., Turpeinen M., Hokkanen J., Uusitalo J., Bouvier d'Yvoire M., Coecke S. Comparison of metabolic stability and metabolite identification of 55 ECVAM/ICCVAM validation compounds between human and rat liver homogenates and microsomes - a preliminary analysis. Altex 2009, 26:214-222.
86. Pelkonen O., Turpeinen M., Hakkola J., Abass K., Pasanen M., Raunio H., Vähäkangas K. Preservation, induction or incorporation of metabolism into the in vitro cellular system - views to current opportunities and limitations. Toxicol. In Vitro 2013, 27:1578-1583.
87. Poulin P., Haddad S. Toward a new paradigm for the efficient in vitro-in vivo extrapolation of metabolic clearance in humans from hepatocyte data. J. Pharm. Sci. 2013, 102:3239-3251.
88. Prakash C., Shaffer C.L., Nedderman A. Analytical strategies for identifying drug metabolites. Mass Spectrom. Rev. 2007, 26:340-369.
89. Punt A., Freidig A.P., Delatour T., Scholz G., Schilter B., Boersma M.G., van Bladeren P.J., Rietjens I.M.C.M. A physiologically based biokinetic (PBBK) model for estragole bioactivation and detoxification in rat. Toxicol. Appl. Pharmacol. 2008, 231:248-259.
90. Reichl S., Becker K. Cultivation of RPMI 2650 ells as an in-vitro model for human transmucosal nasal drug absorption studies: optimization of selected culture conditions. J. Pharm. Pharmacol. 2012, 64:1621-1630.
91. Richert L., Abadie C., Bonet A., Heyd B., Mantion G., Alexandre E., Bachellier P., Kingston S., Pattenden C., Illouz S., Dennison A., Hoffmann S., Coecke S. Inter-laboratory evaluation of the response of primary human hepatocyte cultures to model CYP inducers - a European centre for validation of alternative methods (ECVAM)-funded pre-validation study. Toxicol. In Vitro 2010, 24:335-345.
92. Rodrigues A.V.M., Rollison H.E., Martin S., Sarda S., Schulz-Utermoehl T., Stahl S., Gustafsson F., Eakins J., Kenna J.G., Wilson I.D. In vitro exploration of potential mechanisms of toxicity of the human hepatotoxic drug fenclozic acid. Arch. Toxicol. 2013, 87:1569-1579.
93. Rostami-Hodjegan A., Tucker G.T. Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nat. Rev. 2007, 6:140-148.
94. Rousu T., Pelkonen O., Tolonen A. Rapid detection and characterization of reactive drug metabolites in vitro using several isotope-labeled trapping agents and ultra-performance liquid chromatography/time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 2009, 23:843-855.
95. Sahi J., Grepper S., Smith C. Hepatocytes as a tool in drug metabolism: transport and safety evaluations in drug discovery. Curr. Drug Discov. Technol. 2010, 7:188-198.
96. Sakatis M.Z., Reese M.J., Harrell A.W., Taylor M.A., Baines I.A., Chen L., Bloomer J.C., Yang E.Y., Ellens H.M., Ambroso J.L., Lovatt C.A., Ayrton A.D., Clarke S.E. Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds. Chem. Res. Toxicol. 2012, 25:2067-2082.
97. Saliem M., Holm F., Bergström Tengzelius R., Jorns C., Nilsson L.-M., Ericzon B.-G., Ellis E., Hovatta O. Improved cryopreservation of human hepatocytes using a new xeno free cryoprotectant solution. World J. Hepatol. 2012, 4:176-183.
98. Sarmento B., Andrade F., Baptista da Silva S., Rodrigues F., das Neves J., Ferreira D. Cell-based in vitro models for predicting drug permeability. Exp. Opin. Drug Metab. 2012, 8:607-621.
99. Schroeder K., Bremm K.D., Alepee N., Bessems J.G.M., Blaauboer B., Boehn S.N., Burek C., Coecke S., Gombau L., Hewitt N.J., Heylings J., Huwyler J., Jaeger M., Jagelavicius M., Jarrett N., Ketelslegers H., Kocina I., Koester J., Kreysa J., Note R., Poth A., Radtke M., Rogiers V., Scheel J., Schulz T., Steinkellner H., Toeroek M., Whelan M., Winkler P., Diembeck W. Report from EPAA workshop: in vitro ADME in safety testing used by EPAA industry sectors. Toxicol. In Vitro 2011, 25:589-604.
100. Sevior D.K., Pelkonen O., Ahokas J.T. Hepatocytes: the powerhouse of biotransformation. Int. J. Biochem. Cell Biol. 2012, 44:257-261.
101. Sinkó B., Garrigues T.M., Balogh G.T., Nagy Z.K., Tsinman O., Avdeef A., Takács-Novák K. Skin-PAMPA: a new method for fast prediction of skin penetration. Eur. J. Pharm. Sci. 2012, 45:698-707.
102. Smith D.A. Evaluation of ADME science: where else can modelling and simulation contribute?. Mol. Pharm. 2013, 10:1162-1170.
103. Sohlenius-Sternbeck A.-K., Afzelius L., Prusis P., Neelissen J., Hoogstraate J., Johansson J., Floby E., Bengtsson A., Gissberg O., Sternbeck J., Petersson C. Evaluation of the human prediction of clearance from hepatocyte and microsome intrinsic clearance for 52 drug compounds. Xenobiotica 2010, 40:637-649.
104. Stéphenne X., Najimi M., Sokal E.M. Hepatocyte cryopreservation: Is it time to change the strategy? World J. Gastroenterol 2010, 16:1-14.
105. Strock, C.J., Qin S., Luithardt, H., Gilbert, J., Tsaioun, K., Metcalfe, P., Thomas, S., Aleo, M., Will, Y.,2012. Use of Physiologically-based pharmacokinetic modeling (PBPK) in conjunction with CellCiphr® HCS to predict compound safety threshold and improve lead optimization. SOT (poster) available at . http://www.cyprotex.com/publicationslibrary/.
106. Swift B., Pfeifer N.D., Brouwer K.L. Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity. Drug Metab. Rev. 2010, 42(3):446-471.
107. Takebe T., Sekine K., Enomura M., Koike H., Kimura M., Ogaeri T., Zhang R.R., Ueno Y., Zheng Y.W., Koike N., Aoyama S., Adachi Y., Taniguchi H. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 2013, 499:481-484.
108. Taniguchi A., Wada K., Ohno M. Development of novel culture system using nano-biotechnology. Yakugaku Zasshi 2010, 130:529-535.
109. Testa B., Pedretti A., Vistoli G. Reactions and enzymes in the metabolism of drugs and other xenobiotics. Drug. Discov. Today 2012, 17:549-560.
110. Thompson R.A., Isin E.M., Li Y., Weaver R., Weidolf L., Wilson I., Claesson A., Page K., Dolgos H., Kenna J.G. Risk assessment and mitigation strategies for reactive metabolites in drug discovery and development. Chem. Biol. Interact. 2011, 192:65-71.
111. Tolonen A., Pelkonen O. Analytical challenges for conducting rapid metabolism characterizatio n for QIVIVE. Toxicology 2015, 332:20-29.
112. Tonnelier A., Coecke S., Zaldivar J.M. Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic model. Arch. Toxicol. 2012, 86:393-403.
113. Tostões R.M., Leite S.B., Serra M., Jensen J., Björquist P., Carrondo M.J.T., Brito C., Alves P.M. Human liver cell spheroids in extended perfusion bioreactor culture for repeated dose drug testing. Hepatology 2012, 55:1227-1236.
114. Turco L., Catone T., Caloni F., Di Consiglio E., Testai E., Stammati A. Caco-2/TC7 cell line characterization for intestinal absorption: how reliable is this in vitro model for the prediction of the oral dose fraction absorbed in human?. Toxicol. In Vitro 2011, 25:13-20.
115. Turpeinen M., Tolonen A., Chesne C., Guillouzo A., Uusitalo J., Pelkonen O. Functional expression, inhibition and induction of CYP enzymes in HepaRG cells. Toxicol. In Vitro 2009, 23:748-753.
116. Vaz R.J., Zamora I., Li Y., Reiling S., Shen J., Cruciani G. The challenges of in silico contributions to drug metabolism in lead optimization. Exp. Opin. Drug Metab. Toxicol. 2010, 6:851-861.
117. Vickers A.E., Fisher R.L. Organ slices for the evaluation of human drug toxicity. Chem. Biol. Interact. 2004, 150:87-96.
118. Vinci B., Duret C., Klieber S., Gerbal-Chaloin S., Sa-Cunha A., Laporte S., Suc B., Maurel P., Ahluwalia A., Daujat-Chavanieu M. Modular bioreactor for primary human hepatocyte culture: medium flow stimulates expression and activity of detoxification genes. Biotechnol. J. 2011, 6:554-564.
119. Wagner I., Materne E.-M., Brincker S., Süßbier U., Frädrich C., Busek M., Sonntag F., Sakharov D.A., Trushkin E.V., Tonevitsky A.G., Lauster R., Marx U. A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. Lab. Chip 2013, 13:3538-3547.
120. Wetmore B.A., Wambaugh J.F., Ferguson S.S., Sochaski M.A., Rotroff D.M., Freeman K., Clewell H.J., Ix D.J., Andersen M.E., Houck K.A., Allen B., Judson R.S., Singh R., Kavlock R.J., Richard A.M., Thomas R.S. Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment. Toxicol. Sci. 2012, 125:157-174.
121. Wetmore B.A., Wambaugh J.F., Ferguson S.S., Li L., Clewell H.J., Judson R.S., Freeman K., Bao W., Sochaski M.A., Chu T.M., Black M.B., Healy E., Allen B., Anderson M.E., Wolfinger R.D., Thomas R.S. The relative impact of incorporating pharmacokinetics on predicting in vivo hazard and mode-of-action from high-throughput in vitro toxicity assays. Toxicol. Sci. 2013, 132:327-346.
122. Williams F.M. Potential for metabolism locally in the skin of dermally absorbed compounds. Hum. Exp. Toxicol. 2008, 27:277-280.
123. Wright P. Metabolite identification by mass spectrometry: forty years of evolution. Xenobiotica 2011, 41:670-686.
124. Yang H., Roth C.M., Ierapetritou M.G. A rational design approach for amino acid supplementation in hepatocyte culture. Biotechnol. Bioeng. 2009, 103:1176-1191.
125. Yang H., Roth C.M., Ierapetritou M.G. Analysis of amino acid supplementation effects on hepatocyte cultures using flux balance analysis. OMICS 2011, 15:449-460.
126. Yoon M., Campbell J.L., Andersen M.E., Clewell H. Quantitative in vitro to in vivo extrapolation of cell-based toxicity results. Crit. Rev. Toxicol. 2012, 42:633-652.
127. Zahno A., Brecht K., Morand R., Maseneni S., Torok M., Lindinger P.W., Krahenbuhl S. The role of CYP3A4 in amiodarone associated toxicity on HepG2 cells. Biochem. Pharmacol. 2011, 81:432-441.
128. Zaldívar J.M., Wambaugh J., Judson R. Modelling in vitro cell-based assays experiments: cell population dynamics. Models of the Ecological Hierarchy: From Molecules to the Ecosphere. Developments in Environmental Modelling 2012, 25:51-71. Elsevier.
129. Zanelli U., Caradonna N.P., Hallifax D., Turlizzi E., Houston J.B. Comparison of cryopreserved HepaRG cells with cryopreserved human hepatocytes for prediction of clearance for 26 drugs. Drug Metab. Dispos. 2012, 40:104-110.
130. Zanger U.M., Schwab M. Cytochrome P450 enzymes in drug metabolism regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol. Ther. 2013, 138:103-141.
131. Zanger U.M., Turpeinen M., Klein K., Schwab M. Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal. Bioanal. Chem. 2008, 392:1093-1108.
132. Zeilinger K., Schreiter T., Darnell M., Soderdahl T., Lubberstedt M., Dillner B., Knobeloch D., Nussler A.K., Gerlach J.C., Andersson T.B. Scaling down of a clinical three-dimensional perfusion multicompartment hollow fiber liver bioreactor developed for extracorporeal liver support to an analytical scale device useful for hepatic pharmacological in vitro studies. Tissue Eng. C. Meth. 2011, 17:549-556.