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系統識別號 U0026-0812200914224760
論文名稱(中文) 針對有機陰離子運輸器(OATP)的基因多型性來比較降血壓藥物-血管張力素II拮抗劑(ARB)降壓效果
論文名稱(英文) Comparison of Antihypertensive Effect of Angiotensin II Type I Receptor Antagonists in Subjects with Genetic Polymorphism of OATP
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 96
學期 2
出版年 97
研究生(中文) 黃室瑋
研究生(英文) Shih-Wei Huang
學號 s2695405
學位類別 碩士
語文別 中文
論文頁數 94頁
口試委員 指導教授-黃金鼎
指導教授-賴明亮
口試委員-李惠玲
中文關鍵字 降壓藥物  有機陰離子運輸器 
英文關鍵字 blood pressure  OATP  ARB 
學科別分類
中文摘要 血管收縮素II拮抗劑(Angiotensin II type I receptor antagonist)是新一代的降血壓藥。已上市者包括valsartan, losartan, irbesartan, telmisartan, olmesartan, candesartan, eprosartan。這一類藥品一般而言相當安全有效,但價格非常昂貴。如果能以藥物基因體學的方法來判斷那一類病人適合那一種藥,可以改善高血壓的治療並降低社會成本。這一類藥品目前發現它們的receptor雖然相同,但藥品動態性質有異。雖同是OATP族運輸器(transporter)的受質,但主要的transporter因藥而異。因此,在經過人體試驗委員會通過之後,本試驗招募了受試者62人,並在獲得受試者同意書後,觀察他們的服用五種藥品valsartan, losartan, irbesartan, telmisartan, olmesartan,其降血壓效果是否一致。如果藥與藥之間的效果有別,也就是有人只對其中一兩種藥品特別有效或無效,本計畫將探討其OATP族transporter的基因多型性是否足以解釋個體對此類藥品的差異。其中,OATP1B1的基因型有19個人為帶有*15的受試者,其餘的則沒有帶有*15的受試者;另外,我們也分析了OATP1B3和OATP2B1的基因型。接下來,我們進行multiple regression來探討除了OATP族運輸器的基因多型性,也考慮了性別、年齡、BMI對於血管收縮素II拮抗劑降壓效果的影響。結果發現,除了性別對於telmisartan及losartan的降壓效果有影響,也發現年齡對losartan、olmesartan及irbesartan的藥效有影響之外,也顯示OATP1B3的基因型對於losartan的降壓效果有影響,而OATP2B1的基因型則在對olmesartan的藥效有差異。然而,卻沒有看到OATP1B1的基因型,對於這類降血壓藥物的降壓效果有明顯的影響。
英文摘要 Angiotensin II type I receptor antagonists are now widely in hypertension pharmacotherapy. The angiotensin receptor blockers (ARB), including valsartan, losartan, irbesartan, telmisartan, candesartan, olmesartan, eprosartan, are substrates of OATP transporters. These drugs are in general effective and safe, but they have difference in selectivity of hepatic uptake transporters. To a patient who has poor response to an ARB, a larger dose is often prescribed. We postulated that OATP polymorphism may affect drug response of certain ARB's. If a pharmacogenetic (genotyping or phenotyping) method can be used to find that the poor response is due to OATP SNP's, other ARB's or other classes of antihypertensive can be used instead to obtain a good control of blood pressure. To study the inter-individual variation of ARB's, after the protocol reviewed by NCKU IRB, we have recruited 62 healthy volunteers for pharmacodynamic studies. Five ARB's, valsartan, losartan, irbesartan, telmisartan, olmesartan were given in separate occasions. Blood pressure response was measured after dosing. The relative response of five ARB's was statistics by multiple regression. Among them, 19 subjects carried at least one OATP1B1*15 allele and 43 subjects had either OATP1B1 *1a or *1b allele. Additionally, we also analysis SNP of OATP1B3 and OATP2B1. We found that had significant difference response to olmesartan between subjects with SNP of OATP2B1 and losartan between subjects with SNP of OATP1B3. However, we didn’t found that had a significant difference response to the five ARBs between subjects with SNP of OATP1B1. Additionally, we also found that had significant difference response to certain ARBs with gender and age difference.
論文目次 中文摘要 I
英文摘要 II
目錄 III
表目錄 IV
圖目錄 V
縮寫簡寫表 VI
第一章 緒論 1
第二章 實驗材料 18
第三章 實驗方法 20
第四章 實驗結果 33
第五章 總結與討論 36
參考文獻 47
自述 94
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