(-)-Epicatechin 在家兔體內之藥物動力學研究
(-)-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 (-)-epicate chin 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 2 0-8000ng/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 (-)-epicatec hin 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。
Pharmacokinetic study of (-)-Epicatechin in rabbits
(-)-Epicatechin is a kind of catechins and commonly presents in green tea and cocoa. (-)-Epicatechin acts a s 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 ph armacological actions, but the pharmacokinetics of (-)-epicatechin has not studied well. The aims of this st udy 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 fl uorescence detector, the excitation and emission wavelengths were set at 280nm and 310nm, for determina tion 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 sim ple 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 (-)-epica techin in rabbits. The plasma concentration-time profile of (-)-epicatechin colud be fitted with two-compart ment model with each dose. There were no significant different in elimination half-life and systemic cleara nce under these doses. The elimination half-life were 51.16±6.42 、 51.72±5.15 、 49.99±10.96min ； sys temic clearance were 53.62±6.27 、 53.04±11.07 、 54.32±10.09mL/min/kg. It indicated that the (-)-epicat echin behaved a dose-independent pharmacokinetics between 5 and 25mg/kg. The area under the curve (A UC) 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 (-)-epicatech in was not significant (F=1.07±0.20). After P.O. administration of 50mg/kg (-)-epicatechin, there were grea t individual variations, and the fraction of absorption was low. The mean absolute bioavailability of (-)-epi catechin 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.
