臺灣博碩士論文加值系統

中文摘要
Omeprazole是一個質子幫浦抑制劑，作用在胃壁細胞，由之防止胃酸的分泌。臨床上用於治療 食道-胃反射疾病、胃潰瘍、 Zollinger-Ellison 綜合病徵。
本研究的目的是比較兩種 omeprazole產品 Biozole錠片劑和 Losec膠囊劑(劑量20 mg)在健康男性之生體可用率。經由測得之血中藥物濃度以 LAGRAM-P PROGRAM計算出相關之藥物動力學參數，以評估兩種產品是否為相等性。
本研究首先改良一個方便及精確的高效液相層析方法去定量血漿中omeprazole的濃度。利用 VERCOPACK INERTSIL 5 ODS 80A(4.6×150mm)管柱，移動相為acetonitrile-0.05M phosphate buffer(30:70 pH=7.5)，以 coumarin為內部標準品，流速為0.65ml/min，偵測波長為302nm。
二種 omeprazole產品( Biozole錠片劑與 Losec膠囊劑)之藥物動力學參數，包括最高血中濃度( Cmax)、到達最高血中濃度時間( Tmax)與曲線下面積( AUC)等無統計上的差異。

Abstract
Omeprazole is a proton-pump inhibitor in gastric parietal cells and thus prevents secretion of gastric acid. It is used for the treatment of gastro-esophageal reflux disease, peptic ulcer and the Zollinger-Ellison syndrome.
The aim of the present study was to evaluate the bioavailability of two different 20 mg omeprazole formulations( Biozole tablets and Losec capsules) by following administiation to 12 healthy subjects under fasting. Using LAGRAM-P PROGRAM to calculated pharmacokinetic parameters, the possible bioequivalency of these two products were determined.
A convenient and precise high-performance liquid chromatographic method involving UV detection was described for determination of omeprazole in plasma. A VERCOPACK INERTSIL 5 ODS 80A (4.6X150 mm) column was used as the stationary phase and the mobile phase consisted of acetonitrile-0.05M phosphate buffer(30:70 pH=7.5) solution at a flow rate of 0.65 ml/min. The monitoring wavelength was set at UV 302 nm. The internal standard(coumarin) and omeprazole was eluted approximately at 14.03 min and 10.99 min, respectively.
There are no significant statistic difference between pharmacokinetic parameters of two products(Biozole tablets and Losec capsules), including the peak concentrations (Cmax), time to peak (Tmax) and area under the curve( AUC).

目錄
內文目錄....................Ⅰ
附表目錄....................Ⅲ
附圖目錄....................Ⅳ
中文摘要....................Ⅴ
英文摘要....................Ⅵ
第一章 緒論.....................1
第二章 總論.....................3
第一節 Omeprazole簡介............3
第二節 Omeprazole的理化特性...5
第三節 藥理活性與臨床應用............7
第四節 定量方法.....................12
第五節 藥物動力學............13
第六節 研究動機及目的............18
第三章 實驗材料與方法............20
第一節 實驗材料.....................20
第二節 實驗方法.....................24
第四章 結果與討論............32
第五章 結論.....................38
附表 ....................39
附圖..............................71
參考文獻..............................87
附表目錄
表1. Summary of Balanced Crossover Study Design.......39
表2. Omeprazole之檢量線............................40
表2-1. Omeprazole分析方法之檢量線...................40
表2-2. 個別受試者之檢量線............................40
表3. HPLC血漿定量分析之確效性試驗...................45
表3-1. Omeprazole在HPLC血漿定量分析之同日精確性試驗.45
表3-2. Omeprazole在HPLC血漿定量分析之異日精確性試驗.46
表3-3. Omeprazole在HPLC血漿定量分析之定量極限.47
表3-4. Omeprazole在HPLC血漿定量分析之相對回收率試驗.47
表3-5. Omeprazole在血漿中於25℃安定性試驗..........48
表3-6. Omeprazole在血漿中於-30℃安定性試驗..........48
表4. Losec及 Biozole之體外溶離度試驗...................49
表4-1. Losec之 omeprazole溶離率(%)...................49
表4-2. Biozole之 omeprazole溶離率(%)..........49
表5. 口服 Losec 20mg膠囊劑之血漿 omeprazole濃度.......50
表6. 口服 Biozole 20mg錠片劑之血漿 omeprazole濃度.....51
表7. 十二位受試者之血漿中 omeprazole平均濃度..........52
表8. 十二位受試者之血漿中 omeprazole濃度..............53
表9. 十二位受試者 HPLC定量分析之藥物動力學參數........59
表10.十二位受試者之平均藥物動力學參數.................60
表11.十二位受試者之藥物動力學參數.....................61
表12.十二位受試者藥物動力學參數比較...................67
表13. Two-way ANOVA 統計學比較........................68
附圖目錄
圖1. 溶離度試驗.......................................71
圖2. Omeprazole之高效液相層析圖.......................72
圖3. 標準血漿檢品濃度曲線.............................73
圖4. 十二位受試者之 omeprazole血中濃度圖..............80
圖5. 血漿中 omeprazole平均濃度圖......................86

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