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    標題: 丹參酮IIA在大白鼠體內藥物動力學之研究
    The Pharmacokinetic Studies of Tanshinone IIA in Rats
    作者: 楊竹茂
    黃正芬
    林南海
    連小茵
    貢獻者: 藥學系
    關鍵字: 丹參
    丹參酮IIA
    大白鼠
    體內藥物動力學
    Danshen
    Tanshinone IIA
    Rats
    Pharmacokinetics
    日期: 2006
    上傳時間: 2009-04-24 13:50:10 (UTC+8)
    摘要: 丹參酮IIA (TS)是唇形科(Labiatae)植物丹參(Salvia miltiorrhiza Bge.)之重要活性成分,在中醫臨床上常被用於冠心病相關症狀之預防與治療。為了瞭解TS經口服給藥後之吸收(absorption)、分佈(distribution)、代謝 (metabolism)及排除(elimination)等體內動態,以作為進行開發各種劑型前的參考,本研究以大白鼠為實驗動物,將TS依體重以餵食管灌食20 mg/kg,在灌食前及灌食後之一定時間,自左頸動脈插管抽血,並以HPLC方法分析血漿中藥物之濃度,再以PCNONLIN專業軟體進行藥物動力學參數之計算分析。依照一階次速率單室模式估計,TS的吸收半衰期[T1/2 (ab)]約為13.74分鐘,達到最高血中濃度的時間(Tmax)約為1.121小時,血中最高濃度(Cmax)約為3.7 μg/ml,排除半衰期(T1/2 (el))約為2.28小時,曲線下面積[AUC (0-24hr) (mg.hr/L)]約為21.008。綜合以上數據,顯示TS以口服給藥後,吸收速率很快,但最高血中濃度偏低,排除半衰期較短,以致於需要頻繁投藥始能維持穩定血中濃度。究其原因可能由於遭受較大的首渡效應(first pass effect)所導致,需要進一步研究以闡明此一假設。然而,為了克服此一缺點,將其開發成穿皮吸收、舌下錠等非經口投藥之新劑型應是合理且可預期的。
    Tanshinone IIA (TS) is an important active component of Danshen, (Salvia miltiorrhiza Bge.; Labiatae ) and has been widely used clinically in the traditional Chinese medicine for the treatment and prevention of coronary heart disease and related syndromes. In order to elucidate the pharmacokinetics including absorption, distribution, metabolism and elimination of TS after oral administration, and to serve as references for the further development of new dosage forms, the experiments were performed on rats by intragastric administration of 20mg/kg through gavage needles. Blood samples were withdrawn from left carotid artery catheter before administration and at definite intervals after dosing, and the plasma levels of TS were quantitatively analyzed by HPLC. Pharmacokinetic parameters were then estimated with the aid of PCNONIN software under one compartment first-order model. The results found that T1/2 (ab), Tmax, Cmax, T1/2 (el) and AUC(0-24hr) were 13.74 min., 1.121 hr., 3.7 μg/ml, 2.28 hr. and 21.008 mg.hr/L, respectively, indicating that TS was rapidly absorbed, however, the peak plasma level and elimination half-life were rather lower and less lengthy, rendered it should be frequently dosed to maintain a steady blood concentra-tion. The causes that lead to the relatively lower bioavailability of TS may be subjected to a significant first-pass effect, and a further study should be performed to illustrate this postulation. However, in order to overcome the disadvantages, development of new parenteral dosage forms (transdermal patch, sublingual tablet, etc.) will be reasonable and expectable.
    Appears in Collections:[嘉南學報] 32 期 (2006)
    [藥學系(所)] 期刊論文

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