| 摘要: | 黃芩湯是由黃芩、芍藥、炙甘草及大棗所組成，臨床上常用於治療腹瀉、慢性結腸炎、細菌性痢疾等胃腸疾病。為進行藥物動力學研究，選取最具有藥理活性的黃芩?、芍藥?及甘草酸為指標成分。在本研究中開發出同時分析三種成分的血漿中濃度HPLC定量法。利用Inertsil ODS-2（4.6´250 mm，5 mm）層析管，移動相為乙?與水(85%磷酸調pH 3.45-3.50)之不同比例，以梯度方式進行（0-13 min, 15：85 ® 34：66；13-25 min, 34：66；25-28 min, 34：66 ® 60：40；28-40 min, 60：40），流速1.0 ml/min，以對羥苯甲酸甲酯(methylparaben)為內標準品，檢測波長分別在230、280及248 nm。確效試驗顯示本法有滿意的精確性與準確性。 以三種指標成分之注射液、黃芩湯注射液及黃芩湯口服液分別在六隻家兔進行藥物動力學研究。家兔在靜脈注射黃芩湯後，血漿中之黃芩?、芍藥?及甘草酸濃度皆符合二室體模式。家兔在給予黃芩湯注射液後與指標成分注射液之結果比較，發現黃芩?的排除半衰期速率延長（由62.9±9.3 min增為90.3±12.6 min），芍藥?的排除半衰期速率縮短（由34.9±4.1 min減為27.1±3.2 min）。甘草酸的排除半衰期速率縮短（由206.3±49.0 min減為137.3±7.1 min）。家兔口服黃芩湯後進行藥動學及統計學分析還有生體可用率研究，結果口服後指標成分黃芩?、芍藥?及甘草酸之生體可用率分別為4.2%、4.6%、2.7%。此研究結果可以提供黃芩湯在製劑控管及臨床用藥研究上的參考。; Huang-Chin-Tang (HCT), a traditional Chinese medicine formulation containing Scutellariae Radix, Paeoniae Radix, Glycyrrhizae Radix and Juiubae Fructus, was widely used in the treatment of diarrhea, chronic enteritis. In this study, the pharmacokinetic and bioavailability of the HCT in the rabbits were evaluated. A simple and sensitive HPLC method involving UV detection was developed for simultaneous determination of active constituents of HCT, including baicalin, paeoniflorin and glycyrrhizic acid in preparations and plasma samples. An Intertsil ODS-2 (4.6´250 mm) column with the mobile phase consisted of CH3CN and H2O-H3PO4 (pH 3.5) was used. The 1 ml/min gradient was follow: 0-13 min, 15:85®34:66; 13-25min, 34:66; 25-28 min, 34:66®60:40; 28-40 min, 60:40. The monitoring wavelength was 230, 280 and 248 nm. After IV administrations of the HCT to rabbits, the pharmacokinetics of these three constituents in rabbits were well fitted to an open two-compartment model. The elimination half-lives of baicalin was prolonged (62.9 vs. 90.3 minutes), paeoniflorin was shorted (34.9 vs. 27.1 minutes) and glycyrrhizic acid was shorted (206.3 vs. 137.3 minutes ) were observed after IV administration of the HCT, by compared with those of pure baicalin, paeoniflorin and glycyrrhizic acid injection after IV administion. After oral administrations of the HCT to rabbits, the absolute bioavailability of baicalin, paeoniflorin and glycyrrhizic acid were 4.2%, 4.6%, 2.7%, respectively, indicated that the poorly absorption of these three constituents from GI tracts in rabbits. The results suggest that repeated doses are necessary for HCT in clinical use. |
