- 學位論文
Nifedipine於台灣族群之藥物動態學研究
Pharmacokinetics of nifedipine in Taiwan residents
摘要
Nifedipine (1,4-Dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylic acid dimethyl ester, NF)為dihydropyridine類鈣離子通道阻斷劑，藥理作用為擴張心肌、冠狀動脈及週邊血管平滑肌，臨床上廣泛應用於高血壓、心絞痛、以及週邊血管疾病如Raynoud’s Phenomenon。NF的藥物動態學特性曾被廣泛的研究與討論，其中Ahsan、Renwick等人的研究結果發現，不同族群間NF之藥品動態具有顯著之差異。但有關於臺灣族群之NF藥品動態學研究則尚未見，由於NF的廣泛用途，也基於臺灣族群人民之福祉，因而衍生了本研究之進行。 本研究採用於台灣進行之藥品生體相等性試驗的數據，集合199位健康男性自願受試者，單次口服投與德國Bayer藥廠生產之NF (Adalat®)10 mg後，根據24小時內藥物血中濃度變化情形，運用non-compartment pharmacokinetics方法以及利用WinNonlin套裝軟體計算NF之藥物動態學參數，Cmax、Tmax、AUC及T1/2，並比較台灣居民與其他族群間之藥動學差異。以Student’s t test進行統計學上之雙尾檢定，訂定p<0.05為具有統計學上之意義。 本研究中，NF於台灣健康男性自願受試者吸收十分迅速，平均Cmax為143.24±53.37 ng/ml，Tmax中位數為0.50 (Q1,0.33~Q3,0.67)小時，平均AUC為297.12±124.62 ng ml-1 h，平均T1/2為3.3±1.8小時。其中不論是AUC、Cmax、T1/2皆比白種人高，且具有統計學上之意義 (p<0.001)。台灣人NF的 AUC及Cmax與日本人相似，顯示國人日本人具有相似的藥物動態學特性。而與白種人比較起來，NF於台灣族群之藥動學在AUC方面與白種人有顯著不同，顯示台灣族群對於NF之代謝有比白種人低的可能性。
並列摘要
Nifedipine (1,4-Dihydro-2,6-dimethyl-4-(2-nitro-phenyl)-3,5- pyridine dicarboxylic acid dimethyl ester, NF) is a dihydropyridine calcium channel blocker. NF has been shown to be an effective and relative well-tolerated treatment for stable, variant and unstable angina, mild to severe hypertension and Raynoud’s phenomenon. Studies on NF pharmacokinetics have been published. It is well known that after oral administration there is great interindividual variability in disposition of NF. According to the published literature of NF, Ahsan and Renwick have found the ethnic differences among several populations. The ethnic differences of NF metabolism have been reported in many studies,however the pharmacokinetics of NF in Taiwan residents has not been studied. We conduted a retrospective review of NF bioequivalence studies which completed in the past five years in Taiwan. One hundred and ninty-nine healthy male volunteers who attend the bioequivalence studies were all within the range of ideal body weight. After an overnight fasting, each subject was given a single capsule containing 10 mg of Adalat® manufactured by Bayer, German, as a reference drug. Pharmacokinetic parameters (Cmax, Tmax, AUC and T1/2) which derived from Adalat® administered were calculated by non-compartmental analysis with WinNonlin® program. The difference of pharmacokinetic between Taiwan residents and other population were evaluated as well. After administration of Adalat®, NF is absorbed very fast, the average Cmax of NF in healthy volunteers in Taiwan residents is 143.2±53.4 ng/ml, AUC is 297.1±124.6 ngml-1h and T1/2 is 3.3±1.8 hr, median of Tmax is 0.5 hr (Q1, 0.33~ Q3, 0.67). Compared to the published literature of NF in other population, the AUC, Cmax, and T1/2 of NF were significantly (p<0.001) higher in Taiwan residents than in Caucasians, however, the AUC and Cmax were similar between Taiwan residents and Japanese. According to the published antimode of AUC distribution, 22.5 ng«h/ml/mg, which proposed by Kleinbloesem, there are 69.3% subjects belong to slow metabolizer in Taiwan residents. From the result above, there may be slower metabolism of NF in Taiwan residents than in Caucasians.
參考文獻
延伸閱讀
- 陳穎儀（2005）。Cephamycin於台灣住院病患之使用趨勢探討〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0011-2903200614041183
- 林瑟宜（1992）。Nifedipine硬膠囊處方之研究〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200714450761
- 高子傑（2016）。探討台灣紫金牛科草藥之抗氧化活性與成分分析〔碩士論文，義守大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0074-2801201622145400
- 項怡平（2003）。利用資料蒐納方法探討Digoxin在台灣之族群藥物動力學研究〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0011-0707200816005652
- 劉玲妤（2004）。A Retrospective Drug Utilization Analysis of Thiazolidinediones in National Taiwan University Hospital〔碩士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2004.01070