(-)-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.
