| 摘要: | 中文摘要 本研究是針對天麻素Gastrodin(GA)及其代謝產物天麻苷元p-hydroxybenzyl alcohol(HBA)此二種成分，進行體內過程的相關藥物動力學研究。除了尋找出可同時定量血漿中GA與HBA之精確性，專一性及靈敏度高的高效液相層析(HPLC)定量分析方法外，並選擇在家兔進行藥物動力學之研究，希望能探討天麻素(GA)及其代謝產物(HBA)之體內動態行為。天麻素以兩種不同劑量(100,200mg/kg)在家兔(N=6)進行靜脈注射之藥物動力學研究，發現天麻素及其代謝產物天麻苷元在家兔體內之經時變化，呈現二室及一室模式。其平均曲線下面積分別為15290.33 ? 298.84 , 30300.13 ? 224 , 2875.28 ? 109.19 和 5032.17 ? 191.16 µg•min/ml. 天麻素口服100mg/kg後及其代謝產物天麻苷元，平均曲線下面積分別為2014.19 ? 58.23 和 241.72 ? 4.10 µg•min/ml.。天麻苷元以三種不同劑量(2,10,50mg/kg)在家兔(N=6)進行靜脈注射之藥物動力學研究，發現天麻苷元的平均曲線下面積分別為124.25 ? 4.91 ,649.43 ? 9.70和3033.39 ? 122.84 µg•min/ml.顯示天麻苷元在家兔靜脈注射2~50mg/kg具線性關係，家兔靜脈注射及口服投與天麻素及天麻苷元之生體可用率實驗結果，天麻素之生體可用率為17%，天麻苷元之生體可用率為91.3%，顯示天麻素之口服吸收差以上結果可提供制劑及臨床參考。; Abstract In this study, a simple and sensitive high-performance liquid chromatographic method was developed for the determination of gastrodin(GA) and its metabolite, p-hydroxybenzyl alcohol(HBA) in rabbit blood. After oral administration of the GA (100mg/kg) to the rabbits, the plasma level-time profiles of GA and its metabolite, HBA was adequately described by a two-compartment open model and one-compartment model, respectively. The mean area under the serum concentration curve (AUC0-∞) were about 2014.19 ? 58.23 and 241.72 ? 4.10 µg•min/ml. The pharmacokinetics of GA in the rabbits after intravenous bolus administration of two doses (100,200mg/kg) , the mean area under the serum concentration curve (AUC0-∞) were about 15290.33 ? 298.84 and 30300.13 ? 224.60 µg•min/ml. As well as its metabolite, HBA was about 2875.28 ? 109.19 and 5032.17 ? 191.16 µg•min/ml. The pharmacokinetic study of HBA(100mg/kg) was designed as oral administration to rabbits. The value of area under the plasma concentration-time curve from time 0 to time infinite (AUC0-∞.) was 6865.31 ? 264.17 µg•min/ml. After IV administration of three doses (2 ,10 and 50 mg/kg)HBA , the mean area under the serum concentration curve (AUC0-∞) was about 124.25 ? 4.91 ,649.43 ? 9.70 and 3033.39 ? 122.84 µg•min/ml. The results also indicated that the pharmacokinetics of HBA after IV administration are linear over 2-50 mg/kg dose range. The bioavailability of gastrodin and HBA were 17 and 91.3%. The method was simple, rapid, highly specific and precise. Due to the sufficient gastrodin and p-hydroxybenzyl alcohol plasma concentration profile, we can obtain a pharmacokinetic study. |
