碩士 / 國立成功大學 / 藥理學研究所 / 96 / 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.
| Identifer | oai:union.ndltd.org:TW/096NCKU5550004 |
| Date | January 2007 |
| Creators | Shih-Wei Huang, 黃室瑋 |
| Contributors | Jin-ding Huang, Ming-Liang Lai, 黃金鼎, 賴明亮 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 94 |
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