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???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
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dc.contributor.advisor | 吳焜裕 | |
dc.contributor.author | Yu-Han Chen | en |
dc.contributor.author | 陳禹翰 | zh_TW |
dc.date.accessioned | 2021-06-08T01:38:37Z | - |
dc.date.copyright | 2017-09-12 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-16 | |
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Armbrecht, H. J., Lakshmi, V. M, Wickstra, J, Hsu, F. F, Zenser, T. V. (2007). Metabolism of a heterocyclic amine colon carcinogen in young and old rats. Drug Metab Dispos, 35(4), 633-639. doi:10.1124/dmd.106.013532 Åshild Andreassen∗, L. M., Rose Vikse, Inger-Lise Steffensen, Arne Mikalsen, Jan Erik Paulsen, Jan Alexander. (2002). One dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induces tumours in Min/+ mice by truncation mutations or LOH in the Apc gene Mutation Research, 157–166. Busquets, R., Jonsson, J. A, Frandsen, H, Puignou, L, Galceran, M. T, Skog, K. (2009). Hollow fibre-supported liquid membrane extraction and LC-MS/MS detection for the analysis of heterocyclic amines in urine samples. Mol Nutr Food Res, 53(12), 1496-1504. doi:10.1002/mnfr.200800577 C. W. Jameson, R. M. L., Shawn Jeter, AnnaLee Sabella (2002). Report on Carcinogens Background Document for Selected Heterocyclic Amines: PhIP, MeIQ, and MeIQx Dolan, L. C., Matulka, R. A, Burdock, G. A. (2010). Naturally occurring food toxins. Toxins (Basel), 2(9), 2289-2332. doi:10.3390/toxins2092289 Fede, J. M., Thakur, A. P, Gooderham, N. J, Turesky, R. J. (2009). Biomonitoring of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and its carcinogenic metabolites in urine. Chem Res Toxicol, 22(6), 1096-1105. doi:10.1021/tx900052c Fu, Y., Zhao, G, Wang, S, Yu, J, Xie, F, Wang, H, Xie, J. (2014). Simultaneous determination of fifteen heterocyclic aromatic amines in the urine of smokers and nonsmokers using ultra-high performance liquid chromatography-tandem mass spectrometry. J Chromatogr A, 1333, 45-53. doi:10.1016/j.chroma.2014.01.057 Gooderham, N. J., Soames, A, Rice, J. C, Boobis, A. R, Davies, D. S. (1991). Distribution and elimination of [2-14C]amino-3,8-dimethylimidazo [4, 5-f] quinoxaline in mice. 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New York: Appleton &Lange. NIEHS. (2005). Selected Heterocylclic Amines. Report on Carcinogens. http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s092vhca.pdf. Nobuyuki Ito, R. H., Katsumi Imaida, Seiko Tamano, Akihiro Hagiwara, Masao Hirose, Masao Hirose. (1997). Carcinogenicity of 2-amino-1-methyl-6-phenylimidazo (4,5-b) pyridine PhIP in the rat. Mutation Research. Robert J. Turesky, R. C. G., Dieter H. Welti,Janique Richoz, Steve H. Leveson, Karen H. Dingley, Kenneth W. Turteltaub, Laurent B. Fay. (1998). Metabolism of the Food-Borne Mutagen 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline in Humans. Chem. Res. Toxicol, 11, 217-225. Schut, H. A., Snyderwine, E. G. (1999). DNA adducts of heterocyclic amine food mutagens: implications for mutagenesis and carcinogenesis. Carcinogenesis, 20(3), 353-368. Silvaggio, T., & Mattison, D. R. (1994). Setting occupational health standards: toxicokinetic differences among and between men and women. J Occup Med, 36(8), 849-854. Soldin, O. P., Mattison, D. R. (2009). Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet, 48(3), 143-157. doi:10.2165/00003088-200948030-00001 Sugimura, T., Wakabayashi, K, Nakagama, H, Nagao, M. (2004). Heterocyclic amines Mutagens carcinogens produced during cooking of meat and fish. Cancer Science, 95(4), 290-299. Turesky, R. J. (2009). In Process-Induced Food Toxicants. Occurrence, Formation, Mitigation, and Health Risks. John Wiley & Sons, pp. 75–115. Turteltaub, K. W., Knize, M. G, Healy, S. K, Tucker, J. D, Felton, J. S. (1989). The metabolic disposition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in the induced mouse. Food Chem Toxicol, 27(10), 667-673. US-FDA. (2013). Guidance for Industry Bioanalytical Method Validation Yamaoka, K., Nakagawa, T, Uno, T. (1978). Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. Journal of Pharmacokinetics & Biopharmaceutics, 6(2), 165-175. Zhang, Y. L., Cuiping Fang, Guozhen Mei, Jingbo Wang, Xiao Wang, Shuo. (2011). Tandem solid phase extraction coupled to LC–ESI–MS/MS for the accurate simultaneous determination of five heterocyclic aromatic amines in processed meat products. European Food Research and Technology, 234(2), 197-205. doi:10.1007/s00217-011-1624-4 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18890 | - |
dc.description.abstract | 異環胺為一種高蛋白肉品高溫烹煮後所產生之致癌性化合物,在國人的飲食中皆有暴露的可能,進而對民眾造成致癌風險,為了保障民眾食的安全的必須建構一個客觀的風險評估,因此本研究利用動物模式求得異環胺中2-胺基-3-甲基咪唑[4,5-f]喹啉在大鼠體內的藥物動力學參數,進而了解大鼠在暴露2-胺基-3-甲基咪唑[4,5-f]喹啉後在體內的代謝情形以作為後續風險評估上的運用。而回述相關文獻,目前國際上未有異環胺藥物動力學的相關研究,因此本實驗選擇在眾多異環胺中在IRAC中被歸類為group 2A之2-胺基-3-甲基咪唑[4,5-f]喹啉當作本次實驗的研究物質。
本研究之目的為利用高效液相層析串聯質譜儀建立2-胺基-3-甲基咪唑[4,5-f]喹啉於大鼠血液中的偵測方法,並利用此分析方法,在大鼠動物模式的架構下,探討2-胺基-3-甲基咪唑[4,5-f]喹啉之藥物動力學並比較藥物動力學在公母鼠性別中的差異。本研究符合美國食品藥物管理局的建議規範,方法確效包括了線性、精確性、準確性、基質效應、萃取回收率、以及安定性的評估。 實驗結果顯示公母大鼠靜脈給予10 mg/kg以及口胃給予5 mg/kg、10 mg/kg,其中所得到公鼠平均半衰期分別為117.9 ± 49.7、77.98 ± 9.84、118.1 ± 76.5分鐘;母鼠平均半衰期分別為66.73 ± 28.9、157.5 ± 99.9、129.8 ± 68.0分鐘。此外2-胺基-3-甲基咪唑[4,5-f]喹啉在公鼠口胃給予5 mg/kg、10 mg/kg的劑量下之平均口服生體可用率分別為29.36 ± 6.80、27.2 ± 9.1 %;而在母鼠的中的平均口服生體可用率分別為6.43 ± 2.66、13.26 ± 3.41 %。 研究結果發現,由於2-胺基-3-甲基咪唑[4,5-f]喹啉之親水性在吸收後傾向分布細胞外液,而在公鼠的廓清率較母鼠來的高,在公鼠口胃給予5和10 mg/kg之間有線性藥物動力學關係;母鼠則在口胃給予5和10 mg/kg劑量之間呈現非線性藥物動力學的現象。暴露2-胺基-3-甲基咪唑[4,5-f]喹啉後在公鼠體內有較高的生體可用率,推斷原因是公母鼠肝臟P450細胞色素中的CYP1A2酵素活性差異所致。希望此研究成果能作為後續風險評估之參考依據。 | zh_TW |
dc.description.abstract | Heterocyclic amines (HCAs) are potent carcinogens to which humans are frequently exposed through the consumption of cooked meat and fish food. Thus, a risk assessment needs to be established to minimize the cancer risk. This study used animal model to obtain and understand the pharmacokinetics of 2-Amino-3-methyl-3H-imidazo[4,5-f] quinolone in rats and apply that to risk assessment. Nevertheless, the pharmacokinetic studies of 2-Amino-3-methyl-3H-imidazo[4,5-f] quinolone have not been fully investigated. Thus, this study chose 2-Amino-3-methyl-3H-imidazo[4,5-f] quinolone (IQ), classified as Group 2A in IARC, in our study.
The aim of the study is to develop a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method to determine 2-Amino-3-methyl-3Himidazo[4,5-f] quinolone and discuss the difference of pharmacokinetic between male and female rats. Method validation, including linearity, accuracy, precision, matrix effect, recovery, and stability, is recommended by the U.S. Food and Drug Administration (US-FDA). The result indicated that after the administration of IQ in male rats, the average elimination half-lives of one intravenous (10mg/kg) and two oral dose (5mg/kg and 10mg/kg) are 117.9 ± 49.7, 77.98 ± 9.84 and 118.1 ± 76.5 min, respectively; the average elimination half-lives of one intravenous (10mg/kg) and two oral dose (5mg/kg and 10mg/kg) in female are 66.73 ± 28.9, 157.5 ± 99.9 and 129.8 ± 68.0 min,respectively. Besides, the oral bioavailability of two oral dose (5mg/kg and 10mg/kg) in male rats are 29.36 ± 6.80 % and 27.2 ± 9.1 %;the oral bioavailability of two oral dose (5mg/kg and 10mg/kg) in female rats are 6.43 ± 2.66 and 13.26 ± 3.41 %. Our finding reveals that IQ tends to distribute in extracellular fluid. The clearance rate in male rats is higher than female rats. Linear pharmacokinetics are found between two oral dose (5mg/kg and 10mg/kg) in male rats; nonlinear pharmacokinetics are found between two oral dose (5mg/kg and 10mg/kg) in female rats. We speculate that the difference of activity of CYP1A2 enzyme in the liver of rats is the main reason to cause the oral bioavailability in male rats are higher than in female rats. Our finding will help to determine the further studies of risk assessment. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:38:37Z (GMT). No. of bitstreams: 1 ntu-105-R03841013-1.pdf: 4836751 bytes, checksum: dd0b83090de85913b4bdd5ede267ec96 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 中文摘要 ii
Abstract iv 第一章 背景介紹 1 第二章 研究動機與目的 18 第三章 實驗材料與方法 19 第四章 研究結果 31 第五章 實驗討論 37 第六章 結論 41 第七章 參考文獻 42 | |
dc.language.iso | zh-TW | |
dc.title | "2-胺基-3-甲基咪唑[4,5-f]喹啉在大鼠體內藥物動力學之探討" | zh_TW |
dc.title | Pharmacokinetics of 2-Amino-3-methyl-imidazo[4,5-f]-quinoline in Rats | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 鄭尊仁 | |
dc.contributor.oralexamcommittee | 蔡東湖 | |
dc.subject.keyword | 異環胺,2-胺基-3-甲基咪唑[4,5-f]??,藥物動力學,高效液相層析串聯,生體可用率,廓清率,線性藥物動力學,CYP1A2, | zh_TW |
dc.subject.keyword | Herterocyclic amine,2-Amino-3-methyl-3H-imidazo[4,5-f]quinolone,HPLC-MS/MS,pharmacokinetics,clearance,oral bioavailability,CYP2A1, | en |
dc.relation.page | 62 | |
dc.identifier.doi | 10.6342/NTU201602768 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2016-08-16 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 職業醫學與工業衛生研究所 | zh_TW |
Appears in Collections: | 職業醫學與工業衛生研究所 |
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