Pharmacokinetic study of (+)-Catechin in rabbits

• Main Authors: Yueh Lin Lee, 李岳霖
• Other Authors: Kuang Yang Hsu
• Format: Others
• Language: zh-TW
• Published: 1994
• Online Access: http://ndltd.ncl.edu.tw/handle/39482456003589472331

碩士 === 台北醫學院 === 藥學研究所 === 82 === (+)-Catechin(3,3',4',5,7-tetrahydroxyflavan)是屬於一種 flavonoid 之化合物,在植物界分佈廣泛,它具有顯著的肝保護作用.目前在歐洲臨床 上口服治療急性濾過性病毒肝炎,及避免肝毒性物質和酒精所引起之肝傷 害.本實驗除了對(+)-Catechin之分析方法及血液內之安定性再探討外並 選擇家兔為實驗動物,以不同途徑之投與方式,包括靜脈投與,腹膜腔內 (intraperitonael)投與以及口服投與,來觀察(+)-Catechin在家兔體內之 藥物動力學的表現, 進一步來探討(+)-Catechin在家兔體內之生體可用 率 (bioavaila- bility).本實驗所使用的分析方法採用固-液抽提 (solid-liquid extraction)的方式,使用aluminum oxide為抽提之物質, 並用螢光檢測器(fluorescence detector),增加分析之靈敏度,最低檢測 濃度可達10ng/ml.選擇八隻家兔靜脈注射三種不同劑量，15、20、30mg/ kg之 (+)-Catechin,在此劑量範圍下呈 Dose Independent之藥物動力學, 其數據處理過程符合二室模式,經由靜脈注射30mg/kg,腹膜腔內投與30mg/ kg與口服100mg/kg之(+)-Catechin於家兔體內的結果得知,其代謝屬於線 性藥物動力學(linear pharmacokinetic),而其生體可用率分別為0.85 ±0.36與 0.02±0.01,顯示(+)-Catechin經由肝門脈吸收後,其肝臟首渡 效應(first pass effct),即通過肝臟時只有15%的藥量會被代謝掉;而口 服投與較高劑量100mg/kg之(+)-Catechin,其生體可用率僅有2% ,其原因 可能是由於藥物在腸胃道時之吸收不佳或代謝太快所導致。 The naturally occurring flavanol,(+)-Catechin(3,3',4',5, 7-tetrahydroxyflavan),which is found widespread in plants has been used to traet acute viral hepatitis and prevent hepatic disorders induced by ethanol or hepatotoxic substance in Europe. Up to now, there were few reports about the phar- macokinetics of (+)-Catechin in human and animals reported. In present syudy, the pharmacokinetic of(+)-Catechin with different doses and administrative routes in rabbits was studied. In analytical study, aluminum oxide was used as solid phase extraction material in solid-liquid extraction process. After extraction, a reverse phase HPLC method with fluorescence detector was developed. Under this chromatogra- phic condition, good linearity of standard curve (range 20~ 8000ng/ml, r=0.9999) of (+)-Catechin was obtained and the detective limitation of (+)-Catechin was 10ng/ml. After three different doses of (+)-Catechin (15,20,30mg/kg), there were no significant differnces between elimination rate constant and dose of I.V. administrated. The AUC (area under curve) obtained from I.V. administration of (+)-Catechin was propor- tional to various doses. This means a dose independant phar- macokinetics of (+)-Catechin in rabbits(Y=1.1299X+3.9029, r=0.9585 p<0.001). The intraperitoneal(30mg/kg) and oral (100mg/kg) administration of (+)-Catechin also showed a linear pharmacokinetics. The bioavailability of intraperitoneal and oral administration were 0.85±0.36 and 0.02±0.01, respectively. This means about 15% of (+)-Catechin may be metabolized by liver(hepatic first pass effect), and the bioavailability of oral administration may result from poor absorption of (+)-Catechin in the gastro- intestinal tract.