The in silico prediction of human-specific metabolites from hepatotoxic drugs

Current Drug Discovery Technologies

Volumn 7, Issue 3, 2010, Pages 170-187

  Valerio Jr , Luis G ^a   Long, Anthony ^b  

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

^b LHASA LIMITED   (United Kingdom)

Author keywords

Alternative methods; Computational drug metabolism; Drug metabolism; Hepatotoxic drugs; In silico method

Indexed keywords

BECLOBRATE; BENOXAPROFEN; DILEVALOL; DRUG METABOLITE; FLOSEQUINAN; GLAFENINE; INDOPROFEN; MOXISYLYTE; NIMESULIDE; NIRIDAZOLE; NOMIFENSINE; PIRPROFEN; PRACTOLOL; TASOSARTAN; TROVAFLOXACIN; XIMELAGATRAN; ZILEUTON; ZOMEPIRAC;

ARTICLE; COMPUTER MODEL; COMPUTER PROGRAM; DRUG METABOLISM; DRUG SAFETY; DRUG SCREENING; DRUG STRUCTURE; HUMAN; LIVER MICROSOME; LIVER TOXICITY; PRIORITY JOURNAL;

EID: 78649579536     PISSN: 15701638     EISSN: None     Source Type: Journal    
DOI: 10.2174/157016310793180567     Document Type: Article

References (71)

1. Park K, Williams DP, Naisbitt DJ, Kitteringham NR, Pirmohamed M. Investigation of toxic metabolites during drug development. Toxicol Appl Pharmacol 2005; 207(2, Supplement 1): 425-34.
2. Hastings KL, El-Hage J, Jacobs A, Leighton J, Morse D, Osterberg RE. Letter to the Editor. Toxicol Appl Pharmacol 2003; 190(1): 91-2.
3. Smith DA, Obach RS. Metabolites and safety: What are the concerns, and how should we address them? Chem Res Toxicol 2006; 19(12): 1570-9.
4. FDA. Draft Guidance for Industry: Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling. U.S. FDA, US Dept. Health and Human Services. Rockville, MD USA 2006.
5. Guengerich FP, MacDonald JS. Applying mechanisms of chemical toxicity to predict drug safety. Chem Res Toxicol 2007; 20(3): 344-69.
6. FDA. Guidance for industry: Safety testing of drug metabolites. US Dept. Health and Human Services. Rockville, MD USA 2008.
7. Baillie TA, Cayen MN, Fouda H, et al. Drug METABOLITES IN SAFETY TESTING. Toxicol Appl Pharmacol 2002; 182(3): 188-96.
8. Naito S, Furuta S, Yoshida T, et al. Current Opinion: Safety evaluation of drug metabolites in development of pharmaceuticals. J Toxicol Sci 2007; 32(4): 329-41.
9. Davis-Bruno KL, Atrakchi A. A regulatory perspective on issues and approaches in characterizing human metabolites. Chem Res Toxicol 2006; 19(12): 1561-3.
10. Guengerich FP, MacDonald JS. Applying mechanisms of chemical toxicity to predict drug safety. Chem Res Toxicol 2007; 20(3): 344-69.
11. Waterbeemd H, Gifford E. ADMET in silico modelling: Towards prediction paradise? Nature Reviews Drug Discov 2003; 2: 192-204.
12. Ekins S, Andreyev S, Ryabov A, et al. Computational prediction of human drug metabolism. Expert Opin Drug Metab Toxicol 2005; 1(2): 303-24.
13. Testa B, Balmat, AL, Long, A. Predicting drug metabolism: Concepts and challenges. Pure Appl Chem 2004; 76(5): 907-14.
14. Button WG, Judson PN, Long A, Vessey JD. Using absolute and relative reasing in the prediction of the potential metabolism of xenobiotics. J Chem Inf Model 2003; 43: 1371-7.
15. McGinnity DF, Riley RJ. Predicting drug pharmacokinetics in humans from in vitro metabolism studies. Biochem Soc Trans 2001; 29(2): 135-9.
16. Ursem CJ, Kruhlak NL, Contrera JF, MacLaughlin PM, Benz RD, Matthews EJ. Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans. Part A: Use of FDA post-market reports to create a database of hepatobiliary and urinary tract toxicities. Regul Toxicol Pharmacol 2009; 54(1): 1-22.
17. Grindel JM, O'Neill PJ, Yorgey KA, et al. The metabolism of zomepirac sodium. I. Disposition in laboratory animals and man. Drug Metab Dispos 1980; 8(5): 343-8.
18. FDA. Innovation stagnation: Challenge and opportunity on the critical path to new medicinal products. http://www.fda.gov/oc/initiatives/criticalpath/ whitepaper.html. Rockville, MD: US FDA; 2004.
19. Oliva A, Levin R, Behrman R, Woodcock J. Bioinformatics modernization and the critical path to improved benefit-risk assessment of drugs. Drug Inform J 2008; 42: 273-9.
20. Bernard Testa A-LBALPJ. Predicting Drug Metabolism - an evaluation of the expert system METEOR. Chem Biodivers 2005; 2(7): 872-85.
21. Ekins S, Andreyev S, Ryabov A, et al. A combined approach to drug metabolism and toxicity assessment. Drug Metab Dispos 2006; 34(3): 495-503.
22. Boyer S, Arnby CH, Carlsson L, Smith J, Stein V, Glen RC. Reaction site mapping of xenobiotic biotransformations. J Chem Inf Model 2007; 47(2): 583-90.
23. Zamora I, Afzelius L, Cruciani G. Predicting Drug Metabolism: A site of metabolism prediction tool applied to the Cytochrome P450 2C9. J Med Chem 2003; 46(12): 2313-24.
24. Mekenyan OG, Dimitrov SD, Pavlov TS, Veith GD. A systematic approach to simulating metabolism in computational toxicology. I. The TIMES heuristic modelling framework. Curr Pharm Des 2004; 10(11): 1273-93.
25. Ekins S, de Groot MJ, Jones JP. Pharmacophore and threedimensional quantitative structure activity relationship methods for modeling cytochrome P450 active sites. Drug Metab Dispos 2001; 29(7): 936-44.
26. Sorich MJ, McKinnon RA, Miners JO, Winkler DA, Smith PA. Rapid prediction of chemical metabolism by human UDPglucuronosyltransferase isoforms using quantum chemical descriptors derived with the electronegativity equalization method. J Med Chem 2004; 47(21): 5311-7.
27. Jones JP, Mysinger M, Korzekwa KR. Computational models for cytochrome P450: A predictive electronic model for aromatic oxidation and hydrogen atom abstraction. Drug Metab Dispos 2002; 30(1): 7-12.
28. Marechal J-D, Yu J, Brown S, et al. In silico and in vitro screening for inhibition of cytochrome P450 CYP3A4 by comedications commonly used by patients with cancer. Drug Metab Dispos 2006; 34(4): 534-8.
29. Kemp CA, Flanagan JU, VanEldik AJ, et al. Validation of model of cytochrome P450 2d6: An in silico tool for predicting metabolism and inhibition. J Med Chem 2004; 47(22): 5340-6.
30. Saiakhov RD, Klopman G. MultiCASE Expert Systems and the REACH Initiative. Toxicol Mech Methods 2008; 18(2): 159-75.
31. Marchant CA, Briggs KA, Long A. In silico tools for sharing data and knowledge on toxicity and metabolism: Derek for windows, meteor, and vitic. Toxicol Mech Methods 2008; 18(2): 177-87.
32. Darvas F, Marakhazi S, Kormos P, Kulkarni G, Kalasz H, Papp A. Databases and high throughput testing during drug design and development. In: Erhard PE, Ed. Drug Metabolism. Blackwell Science, University Press, Gamburg, GB.; 1999. pp. 237-70.
33. Jaworska J, Dimitrov S, Nikolova N, Mekenyan O. Probabilistic assessment of biodegradability based on metabolic pathways: CATABOL System. SAR QSAR Environ Res 2002; 13(2): 307-23.
34. Borodina Y, Sadym A, Filimonov D, Blinova V, Dmitriev A, Poroikov V. Predicting biotransformation potential from molecular structure. J Chem Inf Comput Sci 2003; 43(5): 1636-46.
35. Hawkins DR. Use and value of metabolism databases. Drug Discov Today 1999; 4(10): 466-71.
36. Balakin KV, Ekins S, Bugrim A, et al. Quantitative structuremetabolism relationship modeling of metabolic N-dealkylation reaction rates. Drug Metab Dispos 2004; 32(10): 1111-20.
37. Hou BK, Wackett LP, Ellis LBM. Microbial pathway prediction: A functional group approach. J Chem Inf Comput Sci 2003; 43(3): 1051-7.
38. Cruciani G, Carosati E, De Boeck B, et al. MetaSite: Understanding metabolism in human cytochromes from the perspective of the chemist. J Med Chem 2005; 48(22): 6970-9.
39. Hewett M, Oliver DE, Rubin DL, et al. PharmGKB: The pharmacogenetics knowledge base. Nucl Acids Res 2002; 30(1): 163-5.
40. Roth VW, Prox,A., Ifflaender,U. Untersuchungen zur metabolisierung Von beclobrat bei ratte und mensch. Arzneim-Forsch/Drug Res 1985; 35(1): 244-6.
41. Smith GL, Goulbourn RA, Burt RAP, Chatfield DH. Preliminary studies of absorption and excretion of benoxaprofen in man. Br J Clin Pharm 1977; 4: 585-90.
42. Chatfield DH, Green JN. Disposition and metabolism of benoxaprofen in laboratory animals and man. Xenobiotica 1978; 8(3): 133-44.
43. Mohri K, Okada K, Benet LZ. Stereoselective metabolism of benoxaprofen in rats. biliary excretion of benoxaprofen taurine conjugate and glucuronide. Drug Metab Dispos 1998; 26(4): 332-7.
44. Alton KB, Chan TM, Pramanik BN. Urinary metabolites of (R), (R)-labetalol. Drug Metab Dispos 1994; 22(6): 866-72.
45. Kashiyama E, Yokoi T, Odomi M, Funae Y, Inoue K, Kamataki T. Cytochrome P450 responsible for the stereoselective s-oxidation of flosequinan in hepatic microsomes from rats and humans. Drug Metab Dispos 1997; 25(6): 716-24.
46. Kashiyama E, Odomi, M., Shimizu, T. Sterospecific and simultaneous high-performance liquid chromatographic assay of flosequinan and its metabolites in human plasma. J Chromatogr 1994; 52: 179-85.
47. Pottier J, Busigny M, Raynaud JP. Biotransformations of glafenine in the rat and in man. Eur J Drug Metab Pharmacokinet 1979; 2: 109-15.
48. Lund B, Egsmose, C., Knudsen, O., Andersen,R.B. Pharmacokinetic profile of indoprofen in elderly subjects. Br J Clin Pharmacol 1986; 22: 721-4.
49. Fuccella LM, Goldaniga GC, Moro E, Tamassia V, Tosolini GP, Valzelli G. Fate of the analgesic and anti-inflammatory drug K 4277 after oral administration to man. Eur J Clin Pharmacol 1973; 6: 256-60.
50. Marquer C, Bressolle F. High-performance liquid chromatographic determination of the conjugate metabolites of moxisylyte in human plasma and urine. J Chromatogr B Biomed Sci Appl 1997; 691(2): 389-96.
51. Bressolle F, Costa P, Rouzier-Panis R, Marquer C. Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol 1996; 49: 411-5.
52. Carini M, Aldini G, Stefani R, Marinello C, Maffei Facino R. Mass spectrometric characterization and HPLC determination of the main urinary metabolites of nimesulide in man. J Pharm Biomed Anal 1998; 18(1-2): 201-11.
53. Gandini R, Montalto C, Castoldi D, et al. First dose and steady state pharmacokinetics of nimesulide and its 4-hydroxy metabolite in healthy volunteers. Farmaco 1991; 46(9): 1071-9.
54. Sarkar P, McIntosh JM, Leavitt R, Gouthro H. A unique metabolite of nimesulide. J Anal Toxicol 1997; 21: 197-202.
55. Valencia CI, Catto BA, Fairchild EH, Wilson SB, Maramba NC, Webster LT, Jr. Concentration-time course of niridazole and six metabolites in the serum of four Filipinos with Schistosoma japonicum infection. J Pharmacol Exp Ther 1984; 230(1): 133-40.
56. Faigle JW, Blair DM, Clarke VV, Davidson LAG, Dukes DC. Keberle H. The metabolism of niridazole (Ambilhar®) in man. I. Investigations on patients suffering from clinically mild forms of Schistosoma haematobium and Schistosoma mansoni infection. Ann Trop Med Parasitol 1970; 64(3): 373-82.
57. Heptner W, Hornke I, Cavagna F, Fehlhaber HW, Rupp W, Neubauer HP. Metabolism of nomifensine in man and animal species. Arzneim-Forsch/Drug Res 1978; 28(1): 58-64.
58. Lindberg RLP. Selective and sensitive high-performance liquid chromatographic assay for the metabolites of nomifensine in human plasma. J Chromatogr 1985; 341: 333-9.
59. Hornke I, Fehlhaber HW, Girg M, Jantz H. Metabolism of nomifensine (Alival®, Merital®): Isolation and identification of the conjugates of nomifensine-14C from human urine. Br J Clin Pharmac 1980; 9: 255-64.
60. Egger H, Bartlett F, Yuan HP, Karliner J. Metabolism of pirprofen in man, monkey, rat, and mouse. Drug Metab Dispos 1982; 10(5): 529-36.
61. Reeves PR, Case DE, Jepson HT, et al. Practolol metabolism. II. Metabolism in human subjects. J Pharmacol Exp Ther 1978; 205(2): 489-98.
62. Scales B, Cosgrove MB. The metabolism and distribution of the selective adrenergic beta blocking agent, practolol. J Pharmacol Exp Ther 1970; 175(2): 338-47.
63. Elokdah HM, Friedrichs GS, Chai S-Y, et al. Novel human metabolites of the angiotensin-II antagonist tasosartan and their pharmacological effects. Bioorg Med Chem Lett 2002; 12(15): 1967-71.
64. Ellingboe JW, Collini MD, Quagliato D, et al. Metabolites of the Angiotensin II Antagonist Tasosartan: The Importance of a Second Acidic Group. J Med Chem 1998; 41(22): 4251-60.
65. FDA. NDA 20-7959, and NDA 20-760, Clinical Pharmacology and Biopharmaceutics Review. Rockville, MD USA: U.S. Food and Drug Administration, US Department of Health and Human Services; 1998.
66. Eriksson UG, Bredberg U, Hoffmann K-J, et al. Absorption, Distribution, Metabolism, and Excretion of Ximelagatran, an Oral Direct Thrombin Inhibitor, in Rats, Dogs, and Humans. Drug Metab Dispos 2003; 31(3): 294-305.
67. FDA. NDA 20-471, Clinical Pharmacology and Biopharmaceutics Review. Rockville, MD: U.S. Food and Drug Administration, US Department of Health and Human Services; 1994.
68. Muschek LD, Grindel JM. Review of the pharmacokinetics and metabolism of zomepirac in man and animals. J Clin Pharmacol 1980; 20: 223-9.
69. O'Neill PJ, Yorgey KA, Renzi NL, Williams RL, Benet LZ. Disposition of Zomepirac Sodium in Man. J Clin Pharmacol 1982; 22: 470-6.
70. Grindel JM, O'Neill PJ, Yorgey KA, et al. The metabolism of zomepirac sodium. I. Disposition in laboratory animals and man. Drug Metab Dispos 1980; 8(5): 343-8.
71. Smith PC, McDonagh AF, Benet LZ. Irreversible binding of zomepirac to plasma protein in vitro and in vivo. J Clin Invest 1986; 77: 934-9.