鹽酸川芎嗪在家兔之藥物動力學研究; Pharmacokinetic studies of tetramethylpyrazine hydrochloride in Rabbits

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题名:	鹽酸川芎嗪在家兔之藥物動力學研究;Pharmacokinetic studies of tetramethylpyrazine hydrochloride in Rabbits
作者:	葉尚柏;Shang-Poo Yeh
贡献者:	中國醫藥大學：藥物化學研究所碩士班
关键词:	鹽酸川芎嗪;藥物動力學;tetramethylpyrazine hydrochloride
日期:	2006-05-26
上传时间:	2009-08-13 09:37:15 (UTC+8)
摘要:	鹽酸川芎嗪是中藥川芎根莖中的有效成分，具有抗血小板作用、抗血栓形成、調整血脂及抗動脈粥狀硬化、對肺水腫的預防作用、對肺氣腫的防治作用、抗腫瘤作用、抗氧化作用等藥理活性。本研究係對於鹽酸川芎嗪在家兔體內之藥物動力學進行探討。鹽酸川芎嗪在家兔血漿檢品中之分析，是利用已開發的高效液相層析法進行修改後測定。採用Merck LiChrospher® 100 RP-18e 層析管柱(250×4 mm)，移動相為甲醇:水(50:50)，流速1.0 ml/min，以7-hydroxycoumarin為內部標準品， UV偵測波長為280 nm。最低偵測濃度為0.05 μg/ml，回收率為94 %以上，同日及間日之精確性試驗其變異係數(C.V. %)均在10 %以下，故本法可以應用於體液中鹽酸川芎嗪之定量分析。鹽酸川芎嗪以兩種不同劑量(20、40 mg/kg)在六隻家兔進行靜脈注射之藥物動力學研究。發現鹽酸川芎嗪在家兔之經時變化，呈現二室模式。鹽酸川芎嗪的平均半衰期T1/2(β)依次為36.9±2.4、38.6±7.6 min；平均穩定狀態分布體積分別為14.400±1.474與17.286±1.447 L；平均曲線下面積約為238.988 ± 36.633、403.056± 53.573 μg．min/ml。鹽酸川芎嗪以劑量50mg/kg在家兔(N=6)進行口服給藥之藥物動力學研究，發現鹽酸川芎嗪的平均曲線下面積約為201.325±83.254μg．min/ml，平均半衰期T1/2為142.4 min。相關結果可以提供未來製劑學研究及一般使用者吸收方面資料等參考。 Tetramethylpyrazine, an active constituent found in the rhizome of Ligusticum chuanxiong Hort, possesses anti-platelet,anti-atherosclerosis, anti-thrombus synthsis, emphysema prevention, anti-pulmonary edema, anticoagulant, antitumor,and antioxidation effect. In this study, the pharmacokinetics of tetramethylpyrazine in rabbits were evaluated. A simple high performance liquid chromatographic method involving UV detection was modified for determination of tetramethylpyrazine in rabbits plasma. A Merck LiChrospher 100 RP-18e (250×4 mm) column was used as the stationary phase and mobile phase of methanol:water(50:50) and flow rate at 1.0 ml/min, and 7-hydroxycoumarin solution as the internal standard. The UV absorbance was monitored 280nm. The limit of quantitation was 0.05 μg/ml, recovery was 94 %. The coefficient for intraday and interday precison and accuracy was less 10 %. Their data inducates this modified method was enough for a quantitative analysis of tetramethylpyrazine. The pharmacokinetics of tetramethylpyrazine in the rabbit after intravenous bolus administration of various doses (20、40mg/kg) were well described by two compartment open model. The elimination half-lives were 36.9±2.4 and 38.6±7.6 min,respectirely；mean volume of distribution were 14.400±1.474 and 17.286±1.447 L,respectirely；the area under the plasma level-time curve were about 238.988 ± 36.633 and 403.056± 53.573μg．min/ml. ,respectirely The pharmacokinetics of tetramethylpyrazine after oral administration (50mg/kg) to rabbits also exmined. The mean area under the serum concertration curve (AUC) were 201.325±83.25μg．min/ml. The mean half-life (T1/2) were 142.4 min.The oral bioavailability was about 40 %. These result may be useful in support of the dosage forms design and provide to general use information.
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