Cellular models for ADMET predictions and evaluation of drug-drug interactions

Current Opinion in Drug Discovery and Development

Volumn 7, Issue 1, 2004, Pages 86-99

  Riley, Robert J ^a   Kenna, J Gerry ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

ADMET; Cellular models; Drug interactions; Toxicity; Transporters

Indexed keywords

CARRIER PROTEIN; CYTOCHROME P450; ENZYME; DRUG;

CELL FUNCTION; COMPUTER MODEL; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; DRUG RESEARCH; DRUG SCREENING; DRUG UPTAKE; ENZYME INHIBITION; FALSE NEGATIVE RESULT; HUMAN; IN VIVO STUDY; NONHUMAN; PROTEIN EXPRESSION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW; RISK FACTOR; TOXICITY; XENOBIOTIC METABOLISM; ANIMAL; BIOLOGICAL MODEL; CELL LINE; COMPUTER SIMULATION; CYTOLOGY; DRUG INTERACTION; LIVER; METABOLISM; PERMEABILITY; PHARMACOKINETICS;

ANIMALS; CELL LINE; COMPUTER SIMULATION; DRUG INTERACTIONS; HUMANS; LIVER; MODELS, BIOLOGICAL; PERMEABILITY; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS;

EID: 2942537923     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (94)

1. Pharmaceutical Industry 2001 Profile. Pharmaceutical and Manufacturers of America, Washington, DC, USA (2001).
2. Modi S: Computational approaches to the understanding of ADMET properties and problems. Drug Disc Today (2003) 8(14):621-623.
3. Hodgson J: ADMET - turning chemicals into drugs. Nat Biotechnol (2001) 19(8):722-726.
4. Prentis RA, Lis Y, Walker, SR: Pharmaceutical innovation by the seven UK-owned pharmaceutical companies (1964-1985). Br J Clin Pharmacol (1988) 25(3):387-396.
5. Kennedy T: Managing the drug discovery/development interface. Drug Disc Today (1997) 2(10):436-444.
6. Balimane PV, Chong S, Morrison RA: Current methodologies used for evaluation of intestinal permeability and absorption. J Pharmacol Toxicol Methods (2000) 44(1):301-312. A good overview of absorption methodologies.
7. Chiou WL, Barve A: Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats. Pharm Res (1998) 15(11):1792-1795.
8. Chiou WL, Jeong HY, Chung SM, Wu TC: Evaluation of using dog as an animal model to study the fraction of oral dose absorbed of 43 drugs in humans. Pharm Res (2000) 17(2):135-140.
9. Chiou WL, Buehler PW: Comparison of oral absorption and bioavailability of drugs between monkey and human. Pharm Res (2002) 19(6):868-874.
10. Riley RJ, Martin IJ, Cooper AE: The influence of DMPK as an integrated partner in modern drug discovery. Curr Drug Metab (2002) 3(5):527-550. An up-to-date review of some current trends and challenges in discovery DMPK.
11. Lin JH, Yamazaki M: Role of P-glycoprotein in pharmacokinetics: Clinical implications. Clin Pharmacokin (2003) 42(1):59-98.
12. Li AP: Screening for human ADME/Tox drug properties in drug discovery. Drug Disc Today (2001) 6(7):357-366.
13. Kansy M, Senner F, Gubernator K: Physicochemical high throughput screening: Parallel artificial membrane permeation assay in the description of passive absorption processes. J Med Chem (1998) 41(7):1007-1010.
14. Wessel MD, Jurs PC, Tolan JW, Muskal SM: Prediction of human intestinal absorption of drug compounds from molecular structure. J Chem Inf Comput Sci (1998) 38(4):726-735.
15. Kramer SD: Absorption prediction from physicochemical parameters. Pharm Science Tech Today (1999) 2(9):373-380.
16. Raevsky OA, Schaper KJ: Quantitative estimation of hydrogen bond contribution to permeability and absorption processes of some chemicals and drugs. Eur J Med Chem (1998) 33(10):799-807.
17. Bergstrom CA, Strafford M, Lazorova L, Avdeef A, Luthman K, Artusson P: Absorption classification of oral drugs based on molecular surface properties. J Med Chem (2003) 46(4):558-570.
18. Wenlock MC, Austin RP, Barton P, Davis AM, Leeson PD: A comparison of physiochemical property profiles of development and marketed oral drugs. J Med Chem (2003) 46(7):1250-1256.
19. Watkins PB: The barrier function of CYP3A4 and P-glycoprotein in the small bowel. Adv Drug Deliv Rev (1997) 27(2-3):161-170.
20. van de Waterbeemd H, Smith DA, Jones BC: Lipophilicity in PK design: Methyl, ethyl, futile. J Comput Aided Mol Des (2001) 15(3):273-286.
21. Theil FP, Guentert TW, Haddad S, Poulin P: Utility of physiologically based pharmacokinetic models to drug development and rational drug discovery candidate selection. Toxicol Lett (2003) 138(1-2):29-49. A synopsis of this approach to PK modeling and prediction.
22. Teague SJ, Davis AM, Leeson PD, Oprea T: The design of leadlike computational libraries. Angew Chem Int Ed (1999) 38(24):3743-3748.
23. Mizuno N, Niwa T, Yotsumoto Y, Sugiyama Y: Impact of transporter studies on drug discovery and development. Pharmacol Rev (2003) 55(3):425-461.
24. Kuo SM, Whitby BR, Artusson P, Ziemniak JA: The contribution of intestinal secretion to the dose-dependent absorption of celiprolol. Pharm Res (1994) 11(5):648-653.
25. Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK, Borst P, Nooijen WJ, Beijnen JH, van Tellingen O: Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Nat Acad Sci USA (1997) 94(5):2031-2035.
26. Abel S, Beaumont KC, Crespi CL, Eve MD, Fox L, Hyland R, Jones BC, Muirhead GJ, Smith DA, Venn RF, Walker DK: Potential role for P-glycoprotein in the non-proportional pharmacokinetics of UK-343,664 in man. Xenobiotica (2001) 31(8-9):665-676.
27. Riley RJ: The potential pharmacological and toxicological impact of P450 screening. Curr Opin Drug Discovery Dev (2001) 4(1):45-54.
28. Houston JB: Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance. Biochem Pharmacol (1994) 47(9):1469-1479.
29. Houston JB, Carlile DJ: Prediction of hepatic clearance from microsomes, hepatocytes and liver slices. Drug Metab Rev (1997) 29(4):891-922.
30. Mistry M, Houston JB: Glucuronidation in vitro and in vivo: Comparison of intestinal and hepatic conjugation of morphine, naloxone and buprenorphine. Drug Metab Dispos (1987) 15(5):710-717.
31. Soars MG, Burchell B, Riley RJ: In vitro analysis of human drug glucuronidation and prediction of in vivo metabolic clearance. J Pharmacol Exp Ther (2002) 301(1):382-390.
32. Kumar S, Samuel K, Subramanian R, Braun MP, Steams RA, Chiu SH, Evans DC, Baillie TA: Extrapolation of diclofenac clearance from in vitro microsomal metabolism data: Role of acyl glucuronidation and sequential oxidative metabolism of the acyl glucuronide. J Pharmacol Exp Ther (2002) 303(3):969-978.
33. Soars MG, Ring BJ, Wrighton SA: The effect of incubation conditions on the enzyme kinetics of UDP-glucuronosyltransferases. Drug Metab Dispos (2003) 31(6):762-767.
34. Li AP, Lu C, Brent JA, Pham C, Fackett A, Ruegg CE, Silber PM: Cryopreserved human hepatocytes: Characterization of drug-metabolising enzyme activities and applications in higher throughput screening assays for hepatotoxicity, metabolic stability, and drug-drug interaction potential. Chem Biol Interact (1999) 121(1):17-35.
35. Donato MT, Castell JV: Strategies and molecular probes to investigate the role of cytochrome P450 in drug metabolism. Clin Pharmacokin (2003) 42(2):153-178.
36. di Campli C, Gasbarrani G, Gasbarrani A: A medicine based on cell transplantation - is there a future for treating liver diseases? Aliment Pharmacol Ther (2003) 18(5):473-480.
37. Obach RS: Nonspecific binding to microsomes: Impact on scale-up of in vitro intrinsic clearance to hepatic clearance as assessed through examination of warfarin, imipramine, and propranolol. Drug Metab Dispos (1997) 25(12):1359-1369.
38. Obach RS: Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metab Dispos (1999) 27(11):1350-1359.
39. Austin RP, Barton P, Cockroft SL, Wenlock MC, Riley RJ: The influence of nonspecific microsomal binding on apparent intrinsic clearance, and its prediction from physicochemical properties. Drug Metab Dispos (2002) 30(12):1497-1503.
40. Shibata Y, Takahashi H, Ishii Y: A convenient in vitro screening method for prediciting in vivo drug metabolic clearance using isolated hepatocytes suspended in serum. Drug Metab Dispos (2000) 28(12):1518-1523.
41. Lau YY, Sapidou E, Cui X, White RE, Cheng KC: Development of a novel in vitro model to predict hepatic clearance using fresh, cryopreserved, and sandwich-cultured hepatocytes. Drug Metab Dispos (2002) 30(12):1446-1454.
42. Lave T, Dupin S, Schmitt C, Valles B, Ubeaud G, Chou RC. Jaeck D, Caossolo P: The use of human hepatocytes to select compounds based on their expected hepatic extraction ratios in humans. Pharm Res (1997) 14(2):152-155.
43. Naritomi Y, Terashita S, Kimura S, Suzuki A, Kagayama A, Sugiyama Y: Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans. Drug Metab Dispos (2001) 29(10):1316-1324.
44. Naritomi Y, Terashita S, Kagayama A, Sugiyama Y: Utility of hepatocytes in predicting drug metabolism: Comparison of hepatic intrinsic clearance in rats and humans in vivo and in vitro. Drug Metab Dispos (2003) 31(5):580-588.
45. Lin JH: Applications and limitations of interspecies scaling and in vitro extrapolation in pharmacokinetics. Drug Metab Dispos (1998) 26(12):1202-1212.
46. Sasaki M, Suzuki H, Ito K, Abe T, Sugiyama Y: Transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II cell monolayer expressing both human organic anion-transporting polypeptide (OATP2/SLC21A6) and multidrug resistance-associated protein 2 (MRP2/ABCC2). J Biol Chem (2002) 277(8):6497-6503.
47. Ishizuka H, Konno K, Nagamuna N, Nishimura K, Kouzuki H, Suzuki H, Stieger B, Meier PJ, Sugiyama Y: Transport of temocaprilat into rat hepatocytes: Role of organic anion transporting polypeptide. J Pharmacol Exp Ther (1998) 287(1):37-42.
48. Niinuma K, Kato Y, Suzuki H, Tyson CA, Weizer V, Dabbs JE, Froehlich R, Green CE, Sugiyama Y: Primary active transport of organic anions on bile canalicular membrane in humans. Am J Physiol (1999) 276(5 Pt 1):G1153-G1164.
49. Ishizuka H, Konno K, Shiina T, Naganuma H, Nishimura K, Ito K, Suzuki H, Sugiyama Y: Species differences in the transport activity for organic anions across the bile canalicular membrane. J Pharmacol Exp Ther (1999) 290(3):1324-1330.
50. 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 (1999) 27(11):1225-1231.
51. 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 (1999) 27(3):395-402.
52. Kunze KL, Trager WF: Warfarin-fluconazole III. A rational approach to management of a metabolically based drug interaction. Drug Metab Dispos (1996) 24(4):429-435.
53. Bonnabry P, Sievering J, Leemann T, Dayer P: Predictive modelling of in vivo drug interaction from in vitro data: From theory to a computer-based workbench and its experimental validation. In: Interindividual Variability in Drug Metabolism. Pacifici GM, Pelkonen O (Eds), Taylor & Francis, London, UK (2001):240-268.
54. Black DJ, Kunze KL, Weinkers LC, Gidal BE, Seaton TL, McDonnell ND, Evans JS, Bauwens JE, Trager WF: Warfarin-fluconazole II. A metabolically based drug interaction: In vivo studies. Drug Metab Dispos (1996) 24(4):422-428.
55. Kanamitsu S, Ito K, Sugiyama Y: Quantitative prediction of in vivo drug-drug interactions from in vitro data based on physiological pharmacokinetics: Use of maximum unbound concentration of inhibitor at the inlet to the liver. Pharm Res (2000) 17(3):336-343.
56. Kanamitsu S, Ito K, Green CE, Tyson CA, Shimada N, Sugiyama Y: Prediction of in vivo interaction between triazolam and erythromycin based on in vitro studies using human liver microsomes and recombinant human CYP3A4. Pharm Res (2000) 17(4):419-426.
57. Yao C, Kunze KL, Kharasch ED, Wang Y, Trager WF, Ragueneau I, Levy RH: Fluvoxamine-theophylline interaction: Gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2. Clin Pharmacol Ther (2001) 70(5):415-424.
58. Yao C, Kunze KL, Trager WF, Kharasch ED, Levy RH: Comparison of in vitro and in vivo inhibition potencies of fluvoxamine toward CYP2C19. Drug Metab Dispos (2003) 31(5):565-571.
59. Ubeaud G, Hagenbach J, Vandenschrieck S, Jung L, Koffel JC: In vitro inhibition of simvastatin metabolism in rat and human liver by naringenin. Life Sci (1999) 65(13):1403-1412.
60. Ayrton A, Morgan P: Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica (2001) 31(8-9):469-497. A thorough introduction to an emerging challenge.
61. Rolan PE: Plasma protein binding interactions - why are they still regarded as clinically important? Br J Clin Pharmacol (1994) 37(2):125-128.
62. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (Bsep) evaluated as markers of active transport and inhibition: Evidence for contingent unequal binding sites. Pharm Res (2003) 20(4):537-544.
63. Pajeva IK, Wiese M: Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: Explanation of structural variety (hypothesis). J Med Chem (2002) 10(26):5671-5686.
64. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol (2003) 63(3):489-498.
65. Fuhr U: Induction of drug metabolising enzymes: Pharmacokinetic and toxicological consequences in humans. Clin Pharmacokin (2000) 38(6):493-504.
66. LeCluyse EL: Pregnane X receptor: Molecular basis for species differences in CYP3A induction by xenobiotics. Chem Biol Interact (2001) 134(3):283-289. An excellent overview of PXR, a pivotal regulator of drug metabolism and transport.
67. Lu C, Li AP: Species comparison in P450 induction: Effects of dexamethasone, omeprazole, and rifampin on P450 isoforms 1A and 3A in primary cultured hepatocytes from man, Sprague-Dawley rat, minipig and beagle dog. Chem Biol Interact (2001) 134(3):271-281.
68. Luo G, Cunningham M, Kim S, Bum T, Lin J, Sinz M, Hamilton G, Rizzo C, Jolley S, Gilbert D, Downey A et al: CYP3A4 induction by drugs: Correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab Dispos (2002) 30(7):795-804.
69. Tirona RG, Leake BF, Wolkoff AW, Kim RB: Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther (2003) 304(1):223-228.
70. Waxman DJ: P450 gene induction by structurally diverse xenochemicals: Central role of nuclear receptors CAR, PXR and PPAR. Arch Biochem Biophys (1999) 369(1):11-23.
71. Lee G, Piquette-Miller M: Influence of IL-6 on MDR and MRP-mediated multidrug resistance in human hepatoma cells. Can J Physiol Pharmacol (2001) 79(10):876-884.
72. Lazarou J, Pomeranz BH, Corey PN: Incidence of adverse reactions in hospitalized patients: A meta-analysis of prospective studies. J Am Med Assoc (1998) 279(15):1200-1205.
73. Pritchard JF, Jurima-Romet M, Reimer ML, Mortimer E, Rolfe B, Cayen MN: Making better drugs: Decision gates in non-clinical drug development. Nat Rev Drug Disc (2003) 2(7):542-553.
74. ICH Topic S2A: Genotoxicity: Guidance on specific aspects of regulatory genotoxicity tests for pharmaceuticals. (1995) CPMP/ICH/141/95. http://pharmacos.eudra.org/F2/eudralex/vol-3/pdfs-en/3bs6aen.pdf
75. ICH Topic S2B: Genotoxicity: A standard battery for genotoxicity testing for pharmaceuticals. (1997) CPMP/ICH/174/95. http://www.fda.gov/cder/guidance/ 1856fnl.pdf
76. Reifferscheid G, Heil J: Validation of the SOS/umu test using test results of 486 chemicals and comparison with the Ames test and carcinogenicity data. Mutat Res (1996) 369(3-4):129-145.
77. Hinson JA, Pumford NR, Nelson SD: The role of metabolic activation in drug toxicity. Drug Metab Rev (1994) 26(1-2):395-412.
78. Li AP: A review of the common properties of drugs with idiosyncratic hepatotoxicity and the "multiple determinant hypothesis" for the manifestation of idiosyncratic drug toxicity. Chem Biol Interact (2002) 142(1-2):7-23.
79. Yu H, Adedoyin A: ADMET-Tox in drug discovery: Integration of experimental and computational technologies. Drug Disc Today (2003) 8(18):852-861.
80. 35S-glutathione by rat and human hepatocytes for the quantification of xenobiotic reactive intermediates. Chem Biol Interact (2002) 142(1-2):43-55.
81. Evans SM, Casartelli A, Herreros E, Minnick DT, Day C, George A, Westmoreland C: Development of a high throughput in vitro toxicity screen predictive of high acute in vivo toxic potential. Toxicol in vitro (2001) 15(4-5):579-584.
82. Wang K, Shindoh H, Inoue T, Horii I: Advantages of in vitro cytotoxicity testing by using primary rat hepatocytes in comparison with established cell lines. J Toxicol Sci (2002) 27(3):229-237.
83. Lee WM: Drug-induced hepatotoxicity. N Engl J Med (2003) 349(5):474-485.
84. LeCluyse EL: Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur J Pharm Sci (2001) 13(4):343-368.
85. Rippin SJ, Hagenbuch B. Meier PJ, Stieger B: Cholestatic expression pattern of sinusoidal and canalicular organic anion transport systems in primary cultured rat hepatocytes. Hepatology (2001) 33(4):776-782.
86. Kostrubsky VE, Strim SC, Hanson J, Urda E, Rose K, Burliegh J, Zocharski P, Cai H, Sinclair JF, Sahi J: Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats. Toxicol Sci (2003) 76(1):220-228.
87. Fujita K, Kamataki T: Genetically engineered bacterial cells co-expressing human cytochrome P450 with NADPH-cytochrome P450 reductase: Prediction of metabolism and toxicity of drugs in humans. Drug Metab Pharmacokin (2002) 17(1):1-22.
88. Olinga P, Meijer DK, Slooft MJ, Groothuis GM: Liver slices in in vitro pharmacotoxicology with special reference to the use of human liver tissue. Toxicol In Vitro (1997) 12(1):77-100.
89. Xu J, Ma M, Purcell WM: Characterisation of some cytotoxic endpoints using rat liver and HepG2 spheroids as in vitro models and their application in hepatotoxicity studies. I. Glucose metabolism and enzyme release as cytotoxic markers. Toxicol Appl Pharmacol (2003) 189(2):100-111.
90. Jansen PL, Strautnieks SS, Jacquemin E, Hadchouel M, Sokal EM, Hooiveld GJ, Koning JH, de Jager-Krikken A, Kuipers F, Stellard F, Bijleveld CM et al: Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology (1999) 117(6):1370-1379.
91. Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ: Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology (2000) 118(2):422-430.
92. Funk C, Pantze M, Jehle L, Ponelle C, Scheuermann G, Lazendic M, Gasser R: Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate. Toxicology (2001) 167(1):83-98. A thorough mechanistic investigation into a topical area of toxicology.
93. Berson A, De Beco V, Letteron P, Robin MA, Moreau C, El Kahwaji J, Verthier N, Feldmann G, Fromenty B, Pessayre D: Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology (1998) 114(4):764-774.
94. Fielden MR, Zacharewski TR: Challenges and limitations of gene expression profiling in mechanistic and predictive toxicology. Toxicol Sci (2001) 60(1):6-10.