| 摘要: | 三黃瀉心湯是常用傳統中藥方劑，由黃連、黃芩與大黃所組成。本研究利用高效液相層析方法分析蒽醌類(大黃素、大黃酸、大黃素、大黃酚)、多酚類(黃芩苷、黃芩苷元、漢黃芩苷)及生物鹼(小檗鹼)等成分及其代謝物，探討大白鼠口服三黃瀉心湯與大黃黃芩水煎劑後各成分之代謝動力學。 大白鼠口服水煎劑後，血清於sulfatase、glucuronidase分別酶解之前及之後以HPLC方法定量。結果顯示除了大黃酸有原形存在於血中外，其餘成分皆以結合態代謝物存在。其中硫酸結合態代謝物略多於葡萄糖醛酸結合態。小檗鹼則口服不吸收。 環孢靈臨床上用於治療器官移植之排斥反應，治療指數相當狹窄。本研究探討三黃瀉心湯及其各組成藥材在大白鼠體內對環孢靈動力學之影響。以交叉設計分別予大白鼠單獨口服環孢靈及分別併服小檗鹼、黃連、黃芩及三黃瀉心湯水煎劑。於預定時間點經由心臟採血，利用單株螢光免疫偏極法測定環孢靈血中濃度。結果顯示併服三黃瀉心湯導致環孢靈之血峰濃度顯著降低73%，血藥面積下降49%。環孢靈併服黃連、 黃柏、小檗鹼時，血峰濃度分別降低64%、58% 及86%，血藥面積下降52%、55% 及84%。然而，當環孢靈以靜脈注射，併服三黃瀉心湯時，對其動力學並無顯著影響，因此可推測其交互作用主要發生於吸收部位。 為了確保環孢靈之用藥安全及療效，應避免與三黃瀉心湯及其組成中藥併服。; Sun-Huang-Shel-Shin-Tang (SHST), a popular traditional Chinese medicine prescription, comprises Coptidis Rhizoma (Huang Lien), Scutellariae Radix (Huang Qin), and Rhei Rhizoma (RR, Da Huang). In this study, we attempted to develop an HPLC method for the quantitation of anthraquinones (aloe-emodin, rhein, emodin, chrysophanol), flavonoids (baicalein, baicalin, wogonin) and alkaloids (berberine) in the decoction. Rats were administered SHST and serum was assayed prior to and after hydrolysis with sulfatase and β-glucuronidase, respectively. The results showed that only rhein existed in part as free form, other polyphenols were found predominantly as sulfates and glucuronides in the bloodstream. Berberine was not absorbed in rats. Cyclosporine is a commonly used immunosuppressive agent with narrow therapeutic range. Rats were administered cyclosporine with and without SHST, Huang Lien, Huang Bo and berberine in crossover designs. Blood samples were withdrawn via cardiopuncture at predetermined time points and cyclosporine concentrations were determined by a specific monoclonal fluorescence polarization immunoassay. Our results indicated that coadminstration of SHST decoction decreased Cmax of cyclosporine by 73% and reduced AUC0-12h by 49%. Huang Lein, Huang Bo and berberine significantly decreased Cmax of cyclosporine by 64%, 58% and 86%, and reduced AUC0-9h by 52 %, 55% and 84%, respectively. These results indicated that marked interactions occurred between cyclosporine and decoctions of SHST, Huang Lein and Huang Bo. However, when cyclosporine was given intravenously, the pharmacokinetics of cyclosporine was not affected by oral coadminstration of SHST, indicating that the interaction occurred mainly at the absorption site. In order to ensure the efficacy and safety of cyclosporine, the coadministration of SHST and its component herbs with oral cyclosporine should be avoided. |
