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    題名: Catechin對Levodopa於家兔體內藥物動力學影響之研究
    he Effect of Catechin on the Pharmacokinetic of Levodopa in Rabbits
    作者: 范志鴻
    Fan, Chih-Hung
    關鍵詞: Levodopa;3-O-Methyldopa;藥物動力學;Levodopa;3-O-Methyldopa;Pharmacokinetc
    日期: 2012-06-29
    上傳時間: 2018-11-22 09:53:08 (UTC+8)
    摘要: 目的：
    以口服的方式同時給予家兔catechin及levodopa/carbidopa，研究catechin是否會影響levodopa之藥物動力學。
    方法：
    首先，選取十隻雄性紐西蘭種家兔體重範圍約2.4 ~ 3.3 kg，將levodopa/carbidopa以口服的方式給予三種不同劑量(2/0.5、5/1.25及10/2.5 mg/kg)；另外，再以靜脈注射一種劑量之levodopa/carbidopa (2/0.5 mg/kg)。接著，給予levodopa/carbidopa (5/1.25 mg/kg)分別與三種劑量之catechin (50 mg/kg、100 mg/kg及150 mg/kg)併服。上述試驗皆於投藥後進行採血，以液相層析串聯式質譜儀分析其levodopa及3-O-Methyldopa之血中濃度。
    結果：
    口服levodopa/carbidopa (2/0.5 ~ 10/2.5 mg/kg)之levodopa生體可用率為0.53 ± 0.13 ~ 0.59 ± 0.21。Levodopa代謝成3-O-Methyldopa之比率為0.03 ± 0.01。在levodopa部分，與50 mg/kg、100 mg/kg及150 mg/kg catechin併服時，其Cmax、AUC0-t、AUC0-inf分別增加22% ~ 59%、27% ~ 49% 與24% ~ 46%；3-O-Methyldopa部分，其Cmax、AUC0-t、AUC0-inf分別下降31% ~ 48%、29% ~ 47%與33% ~ 49%。由此可知，catechin對於levodopa之影響程度與給予之劑量有關。
    結論：
    由實驗結果得知，catechin會抑制levodopa經COMT酵素代謝，且抑制效果與劑量成正向關係。由此可推知，服用levodopa藥物時，若與含catechin飲料或食物併服，應會增加levodopa之生體可用率，進而提升其治療效果。

    Aims
    The purpose of study was to investigate the effect of catechin on the pharmacokinetics of levodopa via an oral administration.
    Methods
    The dose-dependent pharmacokinetics of levodopa was studied in rabbits via an oral administration. Three different doses of levodopa/carbidopa (2/0.5、5/1.25 and 10/2.5 mg/kg) were administered to ten rabbits via an oral administration, and one dose of levodopa/carbidopa (2/0.5 mg/kg) was administered via an intravenous with a washout period of 1-week between different doses in crossover treatment protocol. Levodopa/carbidopa were co-administered with three doses of catechin (50 mg/kg、100 mg/kg and 150 mg/kg) via an oral administration to ten rabbits. Blood samples collected after dosing and determination of levodopa and its metabolite, 3-O-Methyldopa in plasma by an HPLC coupled with tandem mass method.
    Results
    The bioavailability of levodopa at dose of 2/0.5 mg/kg ~ 10/2.5 mg/kg was 0.53 ± 0.13 ~ 0.59 ± 0.21. The metabolic ratio of 3-O-Methyldopa at all doses were about 0.03 ± 0.01. The Cmax, AUC0-t and AUC0-inf of levodopa at all doses of levodopa/carbidopa increase 22% ~ 59%、27% ~ 49% and 24% ~ 46%, respectively, after co-administered with catechin. The peripheral formation of 3-O-methyldopa also decrease 31% ~ 48%、29% ~ 47% and 33% ~ 49%, respectively. By the results, we could refer that the influence effect of catechin related with the degree of the given dose.
    Conclusion
    The results show that catechin would inhibit COMT enzyme metabolism in rabbits, and the inhibit effect related with the given dose. We could refer that taking levodopa drug with catechin, would increase levodopa concentration in plasma and get better curative effect.
    描述: 碩士
    指導教授-許光陽
    委員-鮑力恆
    委員-陳世銘
    資料類型: thesis
    顯示於類別:[藥學系] 博碩士論文

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