(-)-Epicatechin 在家兔體內之藥物動力學研究 Pharmacokinetic study of (-)-Epicatechin in rabbits
中文摘要
(-)-Epicatechin 屬於兒茶素的一種，常存在於綠茶及可可中。(-)-Epicatechin 可藉 由清除體內自由基達到抗氧化的作用。(-)-Epicatechin 已被證明具有抗神經細胞 老化、抗癌及降低心血管疾病的發生等作用。雖然(-)-epicatechin 有許多藥理活性 但對於(-)-epicatechin 的藥物動力學研究仍不甚完善。本實驗之目的即為研究(-)- epicatechin 於家兔體內之藥物動力學表現。
利用高效液相層析儀，使用C18 的逆相層析管柱，配合螢光偵測器，激發波長
及發射波長分別設在280nm、310nm 下，偵測兔血漿中的(-)-epicatechin 濃度。在
血漿濃度20-8000ng/mL 的範圍內呈現良好的線性，變異係數皆小於 9%。且檢品
處理方法簡單-僅除蛋白，其平均回收率為 87.11±0.03%。
此分析方法亦成功應用於分析(-)-epicatechin 的藥物動力學研究上，以三種不同 劑量，5、10、25mg/kg 之 EC 靜脈投與於家兔體內，分析其血中濃度與時間關係，
顯示(-)-epicatechin 於家兔體內動態符合二室性模式。在排除半衰期與清除率無 統計上之差異，排除半衰期分別為51.16±6.42、51.72±5.15、49.99±10.96min；清 除率分別為53.62±6.27、53.04±11.07、54.32±10.09mL/min/kg。即(-)-epicatechin 在 5-25mg/kg 的劑量範圍下呈 dose-independent 之藥物動力學。其曲線下面積分別 為94.39±11.77、195.93±42.82、476.74±108.18μg‧min/mL，曲線下面積與劑量之關 係呈線性。
以腹膜腔投與25mg/kg 的(-)-epicatechin，其生體可用率為 1.07±0.20，顯示(-)- epicatechin 受到肝臟首渡效應的影響不大。而於口服投與(-)-epicatechin，其個體
差異性大，其吸收的比率相當低，所得之平均生體可用率為0.04±0.02，其原因
可能是由於藥物在腸胃道中的吸收不好或藥品本身溶解度不佳所致。
英文摘要
(-)-Epicatechin is a kind of catechins and commonly presents in green tea and cocoa.
(-)-Epicatechin acts as antioxidant by scavenging free radicals. (-)-Epicatechin is also demonstrated with anti-neurodegenerative, anti-cancer effect, and reduced the risk of cardiovascular disease. Although (-)-epicatechin has several pharmacological actions, but the pharmacokinetics of (-)-epicatechin has not studied well. The aims of this study are to investigate the pharmacokinetic property of (-)-epicatechin in rabbits.
A high-performance liquid chromatographic method was consisted of a C18 reversed- phase column with fluorescence detector, the excitation and emission wavelengths
were set at 280nm and 310nm, for determination of the (-)-epicatechin in rabbit plasma. The calibration curve of plasma sample showed good linearity with the concentration range of 20 to 8000ng/mL. All coefficients of variance were less than 9%. By a simple protein-denature procedure, the average recovery was 87.11±0.03%.
Application of this method was successfully assessed I.V. administration of 5,10,25mg/kg dose of (-)-epicatechin in rabbits. The plasma concentration-time profile of (-)-epicatechin colud be fitted with two-compartment model with each dose.
There were no significant different in elimination half-life and systemic clearance under these doses. The elimination half-life were
51.16±6.42 、51.72±5.15 、49.99±10.96min；systemic clearance were 53.62±6.27 、53.04±11.07、54.32±10.09mL/min/kg. It indicated that the (-)- epicatechin behaved a dose-independent pharmacokinetics between 5 and 25mg/kg.
The area under the curve (AUC) were 94.39±11.77、195.93±42.82、476.74±108.18μg‧
min/mL. The area under the curve (AUC) were proportional to the dose administered.
In addition, 25mg/kg of (-)-epicatehcin was I.P. administrated to rabbit, the first pass effect of (-)-epicatechin was not significant (F=1.07±0.20). After P.O. administration of 50mg/kg (-)-epicatechin, there were great individual variations, and the fraction of absorption was low. The mean absolute bioavailability of (-)-epicatechin was
0.04±0.02. The poor bioavailability may result from poor absorption of (-)- epicatechin in the gastro-intestinal tract or low solubility of (-)-epicatechin.
