Systems pharmacology modeling: An approach to improving drug safety

Biopharmaceutics and Drug Disposition

Volumn 35, Issue 1, 2014, Pages 1-14

  Bai, Jane P F ^a   Fontana, Robert J ^b   Price, Nathan D ^c   Sangar, Vineet ^c  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^c INSTITUTE FOR SYSTEMS BIOLOGY   (United States)

Author keywords

biomarkers clinical phenotype; cellular phenotype; gene drug interaction; mitochondria; molecular networks; molecular pathways; organ injury; systems biology

Indexed keywords

CELL ORGANELLE; CLINICAL FEATURE; DRUG EFFECT; DRUG EXPOSURE; DRUG SAFETY; GENETIC POLYMORPHISM; HUMAN; IMMUNOSURVEILLANCE; MITOCHONDRIAL TOXICITY; MODEL; NONHUMAN; PHENOTYPE; REVIEW; SYSTEMS PHARMACOLOGY MODELING; TOXICITY;

BIOMARKERS/CLINICAL PHENOTYPE; CELLULAR PHENOTYPE; GENE DRUG INTERACTION; MITOCHONDRIA; MOLECULAR NETWORKS; MOLECULAR PATHWAYS; ORGAN INJURY; SYSTEMS BIOLOGY;

BIOLOGICAL MARKERS; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; HUMANS; MODELS, BIOLOGICAL; PHARMACOLOGY, CLINICAL; PHENOTYPE; SYSTEMS BIOLOGY;

EID: 84892364548     PISSN: 01422782     EISSN: 1099081X     Source Type: Journal    
DOI: 10.1002/bdd.1871     Document Type: Review

References (85)

1. Drugs@FDA. http://wwwaccessdatafdagov/scripts/cder/drugsatfda/indexcfm/ [January 2013 ].
2. Takai N, Tanaka Y, Inazawa K, Saji H,. Quantitative analysis of pharmaceutical drug distribution in multiple organs by imaging mass spectrometry. Rapid Commun Mass Spectrom 2012; 26: 1549-1556. doi: 10.1002/rcm.6256.
3. Hood L, Heath JR, Phelps ME, Lin B,. Systems biology and new technologies enable predictive and preventative medicine. Science 2004; 5696: 640-643. doi: 10.1126/science.1104635.
4. Wagner BK, Kitami T, Gilbert TJ, et al,. Large-scale chemical dissection of mitochondrial function. Nat Biotechnol 2008; 26: 343-351. doi: 10.1038/nbt1387.
5. Morikawa S, Murakami T, Yamazaki H, et al,. Analysis of the global RNA expression profiles of skeletal muscle cells treated with statins. J Atheroscler Thromb 2005; 12: 121-131.
6. Meganathan K, Jagtap S, Wagh V, et al,. Identification of thalidomide-specific transcriptomics and proteomics signatures during differentiation of human embryonic stem cells. PLoS One 2012; 7: e44228. doi: 10.1371/journal.pone.0044228.
7. Bai JP, Abernethy DR,. Systems pharmacology to predict drug toxicity: integration across levels of biological organization. Annu Rev Pharmacol Toxicol 2013; 53: 451-473. doi: 10.1146/annurev-pharmtox-011112-140248.
8. Cundy T, Mackay J,. Proton pump inhibitors and severe hypomagnesaemia. Curr Opin Gastroenterol 2011; 27: 180-185. doi: 10.1097/MOG.0b013e32833ff5d6.
9. Bai JP, Hausman E, Lionberger R, Zhang X,. Modeling and simulation of the effect of proton pump inhibitors on magnesium homeostasis. 1. Oral absorption of magnesium. Mol Pharm 2012; 9: 3495-3505. doi: 10.1021/mp300323q.
10. Michalek W, Semler JR, Kuo B,. Impact of acid suppression on upper gastrointestinal pH and motility. Dig Dis Sci 2011; 56: 1735-1742. doi: 10.1007/s10620-010-1479-8.
11. Krug SM, Gunzel D, Conrad MP, et al,. Charge-selective claudin channels. Ann NY Acad Sci 2012; 1257: 20-28. doi: 10.1111/j.1749-6632.2012.06555.x.
12. 2+ content and estrogens. J Am Soc Nephrol 2006; 17: 1035-1043. doi: 10.1681/ASN.2005070700.
13. 2+ availability. Cell Physiol Biochem 2010; 25: 705-714. doi: 10.1159/000315090.
14. Howell BA, Yang Y, Kumar R, et al,. In vitro to in vivo extrapolation and species response comparisons for drug-induced liver injury (DILI) using DILIsym: a mechanistic, mathematical model of DILI. J Pharmacokinet Pharmacodyn 2012; 39: 527-541. doi: 10.1007/s10928-012-9266-0.
15. Anderson S, Bankier AT, Barrell BG, et al,. Sequence and organization of the human mitochondrial genome. Nature 1981; 290: 457-465.
16. DiMauro S, Schon EA,. Mitochondrial respiratory-chain diseases. N Engl J Med 2003; 348: 2656-2668. doi: 10.1056/NEJMra022567.
17. Laaksonen R, Katajamaa M, Paiva H, et al,. A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle. PLoS One 2006; 1: e97. doi: 10.1371/journal.pone.0000097.
18. Huan T, Zhang B, Wang Z, et al,. A systems biology framework identifies molecular underpinnings of coronary heart disease. Arterioscler Thromb Vasc Biol 2013; 33: 1427-1434. doi: 10.1161/ATVBAHA.112.300112.
19. Pagon RA, Editor-in-chief, Bird TD, Dolan CR, Stephens K, Adam MP,. GeneReviews™. University of Washington: Seattle; 1993-2013.
20. Connectivity Map. http://wwwbroadinstituteorg/genome-bio/ connectivitymaphtml/[ January, 2013 ].
21. Gene Expression Omnibus (GEO). http://wwwncbinlmnihgov/geo/[ January, 2012 ].
22. Hanna AD, Janczura M, Cho E, Dulhunty AF, Beard NA,. Multiple actions of the anthracycline daunorubicin on cardiac ryanodine receptors. Mol Pharmacol 2011; 80: 538-549. doi: 10.1124/mol.111.073478.
23. Mohaupt MG, Karas RH, Babiychuk EB, et al,. Association between statin-associated myopathy and skeletal muscle damage. CMAJ 2009; 181: E11-E18. doi: 10.1503/cmaj.081785.
24. Marciante KD, Durda JP, Heckbert SR, et al,. Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics 2011; 21: 280-288. doi: 10.1097/FPC.0b013e328343dd7d.
25. Kegg pathway Database. http://wwwgenomejp/kegg/kegg1html/[May 2013 ].
26. Kirouac DC, Saez-Rodriguez J, Swantek J, Burke JM, Lauffenburger DA, Sorger PK,. Creating and analyzing pathway and protein interaction compendia for modelling signal transduction networks. BMC Syst Biol 2012; 6: 29. doi: 10.1186/1752-0509-6-29.
27. Table of Pharmacogenomic Biomarkers in Drug Labels. http://wwwfdagov/ Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378htm/[May 2013 ].
28. Chin EL, da Silva C, Hegde M,. Assessment of clinical analytical sensitivity and specificity of next-generation sequencing for detection of simple and complex mutations. BMC Genet 2013; 14: 6. doi: 10.1186/1471-2156-14- 6.
29. Skotland T,. Molecular imaging: challenges of bringing imaging of intracellular targets into common clinical use. Contrast Media Mol Imaging 2012; 7: 1-6. doi: 10.1002/cmmi.458.
30. Bordbar A, Feist AM, Usaite-Black R, Woodcock J, Palsson BO, Famili I,. A multi-tissue type genome-scale metabolic network for analysis of whole-body systems physiology. BMC Syst Biol 2011; 5: 180. doi: 10.1186/1752-0509-5-180.
31. LeMasters JJ, Hepatotoxicity due to mitochondrial injury drug induced liver disease. In Drug-Induced Liver Disease, Kaplowitz N, DeLeve LD, (eds). Marcel Dekker, Inc: New York, 85-97. ISBN: 9780123878175, 2013; 85-97.
32. Martin JL, Brown CE, Matthews-Davis N, Reardon JE,. Effects of antiviral nucleoside analogs on human DNA polymerases and mitochondrial DNA synthesis. Antimicrob Agents Chemother 1994; 38: 2743-2749.
33. Stewart JD, Horvath R, Baruffini E, et al,. Polymerase gamma gene POLG determines the risk of sodium valproate-induced liver toxicity. Hepatology 2010; 52: 1791-1796. doi: 10.1002/hep.23891.
34. Igoudjil A, Massart J, Begriche K, Descatoire V, Robin MA, Fromenty B,. High concentrations of stavudine impair fatty acid oxidation without depleting mitochondrial DNA in cultured rat hepatocytes. Toxicol In Vitro 2008; 22: 887-898. doi: 10.1016/j.tiv.2008.01.011.
35. Robinson MJ, Rywlin AM,. Tetracycline-associated fatty liver in the male. Report of an autopsied case. Am J Dig Dis 1970; 15: 857-862.
36. Bleeker-Rovers CP, Kadir SW, van Leusen R, Richter C,. Hepatic steatosis and lactic acidosis caused by stavudine in an HIV-infected patient. Neth J Med 2000; 57: 190-193.
37. Larosche I, Letteron P, Fromenty B, et al,. Tamoxifen inhibits topoisomerases, depletes mitochondrial DNA, and triggers steatosis in mouse liver. J Pharmacol Exp Ther 2007; 321: 526-535. doi: 10.1124/jpet.106.114546.
38. Freiman JP, Helfert KE, Hamrell MR, Stein DS,. Hepatomegaly with severe steatosis in HIV-seropositive patients. Aids 1993; 7: 379-385.
39. Melegh B, Trombitas K,. Valproate treatment induces lipid globule accumulation with ultrastructural abnormalities of mitochondria in skeletal muscle. Neuropediatrics 1997; 28: 257-261. doi: 10.1055/s-2007-973710.
40. Fujimura H, Murakami N, Kurabe M, Toriumi W,. In vitro assay for drug-induced hepatosteatosis using rat primary hepatocytes, a fluorescent lipid analog and gene expression analysis. J Appl Toxicol 2009; 29: 356-363. doi: 10.1002/jat.1420.
41. Lim SW, Hyoung BJ, Piao SG, Doh KC, Chung BH, Yang CW,. Chronic cyclosporine nephropathy is characterized by excessive autophagosome formation and decreased autophagic clearance. Transplantation 2012; 94: 218-225. doi: 10.1097/TP.0b013e31825ace5c.
42. Zinman L, Sadeghi R, Gawel M, Patton D, Kiss A,. Are statin medications safe in patients with ALS? Amyotroph Lateral Scler 2008; 9: 223-228. doi: 10.1080/17482960802031092.
43. Murinson BB, Haughey NJ, Maragakis NJ,. Selected statins produce rapid spinal motor neuron loss in vitro. BMC Musculoskelet Disord 2012; 3: 100. doi: 10.1186/1471-2474-13-100.
44. Garrabou G, Soriano A, Lopez S, et al,. Reversible inhibition of mitochondrial protein synthesis during linezolid-related hyperlactatemia. Antimicrob Agents Chemother 2007; 51: 962-967. doi: 10.1128/AAC.01190-06.
45. Montaigne D, Hurt C, Neviere R,. Mitochondria death/survival signaling pathways in cardiotoxicity induced by anthracyclines and anticancer-targeted therapies. Biochem Res Int 2012; 2012: 951539. doi: 10.1155/2012/951539.
46. Uyemura SA, Santos AC, Mingatto FE, Jordani MC, Curti C,. Diclofenac sodium and mefenamic acid: potent inducers of the membrane permeability transition in renal cortex mitochondria. Arch Biochem Biophys 1997; 342: 231-235. doi: 10.1006/abbi.1997.9985.
47. Furberg CD, Pitt B,. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med 2001; 2: 205-207.
48. Han D, Shinohara M, Ybanez MD, Saberi B, Kaplowitz N,. Signal transduction path ways involved in drug-induced liver injury. Handb Exp Pharmacol 2010; 196: 267-310. doi: 10.1007/978-3-642-00663-0-10.
49. Fisher JE, McKenzie TJ, Lillegard JB, et al,. Role of Kupffer cells and toll-like receptor 4 in acetaminophen-induced acute liver failure. J Surg Res 2013; 180: 147-155. doi: 10.1016/j.jss.2012.11.051.
50. Oka T, Hikoso S, Yamaguchi O, et al,. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 2012; 485: 251-255. doi: 10.1038/nature10992.
51. Casalena G, Daehn I, Bottinger E,. Transforming growth factor-beta, bioenergetics, and mitochondria in renal disease. Semin Nephrol 2012; 32: 295-303. doi: 10.1016/j.semnephrol.2012.04.009.
52. Xie XL, Wei M, Kakehashi A, Yamano S, Tajiri M, Wanibuchi H,. 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) promotes mouse hepatocarcinogenesis by activating transforming growth factor-beta and Wnt/beta-catenin signaling pathways. Toxicol Sci 2012; 125: 392-400. doi: 10.1093/toxsci/kfr314.
53. Jantzen K, Roursgaard M, Desler C, Loft S, Rasmussen LJ, Moller P,. Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. Mutagenesis 2012; 27: 693-701. doi: 10.1093/mutage/ges035.
54. Hung SI, Chung WH, Jee SH, et al,. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics 2006; 16: 297-306. doi: 10.1097/01.fpc.0000199500.46842.4a.
55. Archer SL, Marsboom G, Kim GH, et al,. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and a new therapeutic target. Circulation 2010; 121: 2661-2671. doi: 10.1161/CIRCULATIONAHA.109.916098.
56. Vockley J, Rinaldo P, Bennett MJ, Matern D, Vladutiu GD,. Synergistic heterozygosity: disease resulting from multiple partial defects in one or more metabolic pathways. Mol Genet Metab 2000; 71: 10-18. doi: 10.1006/mgme.2000. 3066.
57. Kohler S, Bauer S, Horn D, Robinson PN,. Walking the interactome for prioritization of candidate disease genes. Am J Hum Genet 2008; 82: 949-958. doi: 10.1007/s12012-008-9015-1.
58. Warren JD, Blumbergs PC, Thompson PD,. Rhabdomyolysis: a review. Muscle Nerve 2002; 25: 332-347.
59. Bai JP, Lesko LJ, Burckart GJ,. Understanding the genetic basis for adverse drug effects: the calcineurin inhibitors. Pharmacotherapy 2010; 30: 195-209. doi: 10.1592/phco.30.2.195.
60. Sauret JM, Marinides G, Wang GK,. Rhabdomyolysis. Am Fam Physician 2002; 65: 907-912.
61. Kottlors M, Jaksch M, Ketelsen UP, Weiner S, Glocker FX, Lucking CH,. Valproic acid triggers acute rhabdomyolysis in a patient with carnitine palmitoyltransferase type II deficiency. Neuromuscul Disord 2001; 11: 757-759.
62. Vladutiu GD, Simmons Z, Isackson PJ, et al,. Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle Nerve 2006; 34: 153-162. doi: 10.1002/mus.20567.
63. Tujios S, Fontana RJ,. Mechanisms of drug-induced liver injury: from bedside to bench. Nat Rev Gastroenterol Hepatol 2011; 8: 202-211. doi: 10.1038/nrgastro.2011.22.
64. Kossak BD, Schmidt-Sommerfeld E, Schoeller DA, Rinaldo P, Penn D, Tonsgard JH,. Impaired fatty acid oxidation in children on valproic acid and the effect of l -carnitine. Neurology 1993; 43: 2362-2368.
65. Kolodkin A, Simeonidis E, Balling R, Westerhoff HV,. Understanding complexity in neurodegenerative diseases: in silico reconstruction of emergence. Front Physiol 2012; 3: 291. doi: 10.3389/fphys.2012.00291.
66. Carreras MC, Poderoso JJ,. Mitochondrial nitric oxide in the signaling of cell integrated responses. Am J Physiol Cell Physiol 2007; 292: C1569-C1580. doi: 10.1152/ajpcell.00248.2006.
67. de Moura MB, dos Santos LS, Van Houten B,. Mitochondrial dysfunction in neurodegenerative diseases and cancer. Environ Mol Mutagen 2010; 51: 391-405. doi: 10.1002/em.20575.
68. Cohen BH,. Pharmacologic effects on mitochondrial function. Dev Disabil Res Rev 2010; 16: 189-199. doi: 10.1002/ddrr.106.
69. Anastasiou D, Poulogiannis G, Asara JM, et al,. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 2011; 334: 1278-1283. doi: 10.1126/science.1211485.
70. Ames BN,. Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science 1983; 221: 1256-1264.
71. Waris G, Ahsan H,. Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 2006; 5: 14. doi: 10.1186/1477-3163-5-14.
72. Behrend L, Henderson G, Zwacka RM,. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 2003; 31 (6): 1441-1444. doi: 10.1042/.
73. Klaunig JE, Kamendulis LM,. The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 2004; 44: 239-267. doi: 10.1146/annurev.pharmtox.44.101802.121851.
74. Zineh I, Woodcock J,. Clinical pharmacology and the catalysis of regulatory science: opportunities for the advancement of drug development and evaluation. Clin Pharmacol Ther 2013; 93: 515-525. doi: 10.1038/clpt.2013.32.
75. Duarte NC, Becker SA, Jamshidi N, et al,. Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci U S A 2007; 104: 1777-1782. doi: 10.1073/pnas.0610772104.
76. Thiele I, Swainston N, Fleming RM, et al,. A community-driven global reconstruction of human metabolism. Nat Biotechnol 2013; 31: 419-425. doi: 10.1038/nbt.2488.
77. Wang Y, Eddy JA, Price ND,. Reconstruction of genome-scale metabolic models for 126 human tissues using mCADRE. BMC Syst Biol 2012; 6: 153. doi: 10.1186/1752-0509-6-153.
78. Agren R, Bordel S, Mardinoglu A, Pornputtapong N, Nookaew I, Nielsen J,. Reconstruction of genome-scale active metabolic networks for 69 human cell types and 16 cancer types using INIT. PLoS Comput Biol 2012; 8: e1002518. doi: 10.1371/journal.pcbi.1002518.
79. Jerby L, Shlomi T, Ruppin E,. Computational reconstruction of tissue-specific metabolic models: application to human liver metabolism. Mol Syst Biol 2010; 6: 401. doi: 10.1038/msb.2010.56.
80. Forsyth BW, Horwitz RI, Acampora D, et al,. New epidemiologic evidence confirming that bias does not explain the aspirin/Reye's syndrome association. JAMA 1989; 261: 2517-2524.
81. Bryant AE 3rd, Dreifuss FE,. Valproic acid hepatic fatalities. III. U.S. experience since 1986. Neurology 1996; 46: 465-469.
82. McKenzie R, Fried MW, Sallie R, et al,. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N Engl J Med 1995; 333: 1099-1105. doi: 10.1056/NEJM199510263331702.
83. Cornejo-Juarez P, Sierra-Madero J, Volkow-Fernandez P,. Metabolic acidosis and hepatic steatosis in two HIV-infected patients on stavudine (d4T) treatment. Arch Med Res 2003; 34: 64-69.
84. Bissuel F, Bruneel F, Habersetzer F, et al,. Fulminant hepatitis with severe lactate acidosis in HIV-infected patients on didanosine therapy. J Intern Med 1994; 235: 367-371.
85. De Vriese AS, Coster RV, Smet J, et al,. Linezolid-induced inhibition of mitochondrial protein synthesis. Clin Infect Dis 2006; 42: 1111-1117. doi: 10.1086/501356.