Taipei Medical University Institutional Repository:Item 987654321/1555
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    Please use this identifier to cite or link to this item: http://libir.tmu.edu.tw/handle/987654321/1555


    Title: A Dose-dependent Pharmacokinetic Study of Levodopa by Intramuscular Administration in Rabbits
    Authors: 王莉萱;許光陽
    Wang LS;Hsu KY;Hsu FL;Lin SJ
    Contributors: 藥學系
    Date: 2008
    Issue Date: 2009-08-17 09:55:28 (UTC+8)
    Abstract: 本研究爲將levodopa以肌肉注射方式投予家兔，探討levodopa劑量依存性之藥物動力學。以三種不同劑量的L-dopa/carbidopa (2/0.5, 5/1.25, and 10/2.5 mg/kg)經肌肉注射及一種劑量之L-dopa/carbidopa (2/0.5 mg/kg)經靜脈注射，依交叉試驗方式分別投予六隻雄性兔子，在投藥後採血，取血漿樣品並以高壓液相層析儀分析L-dopa及3-O-methyldopa （levodopa之代謝物，3-OMD）之濃度，經由所得之數據決定L-dopa與3-OMD之藥物動力學之模式。由結果得知，L-dopa經肌肉注射後會被快速吸收，並於30分鐘內達到最高濃度，但3-OMD的形成則較慢，須於120-180分後才達到最高點。L-dopa經肌肉注射後之生體可用率爲0.70-1.21，而3-OMD形成之相對比率爲0.79-1.24；另於不同劑量間，L-dopa之肌肉注射生體可用率及3-OMD形成比率不具統計上的差異。此外，L-dopa與3-OMD於排除半衰期上也不具統計上的差異；而在曲線下面積(AUC)及血漿中最高濃度值(Cmax)，L-dopa與3-OMD於L-dopa/carbidopa在2/0.5-10/2.5 mg/kg劑量範圍內亦呈現正比增加之現象。由此可知，L-dopa與3-OMD在此劑量範圍內無劑量依存性之藥物動力學現象。
    The dose-dependent pharmacokinetics of levodopa (L-dopa) was studied in rabbits by intramuscular administration. Three different doses of L-dopa/carbidopa (2/0.5, 5/1.25, and 10/2.5 mg/kg) were administered to six male rabbits via an intramuscular (IM) route, and one dose of L-dopa/carbidopa (2/0.5 mg/kg) was administered via an intravenous (IV) route with a washout period of 1-week between different doses. Plasma samples were collected after each treatment and the concentrations of L-dopa and 3-O-methyldopa (an L-dopa metabolite, 3-OMD) were measured by a sensitive high-performance liquid chromatographic (HPLC) method. Subsequently, these measurements were used to determine the pharmacokinetic behavior of L-dopa and 3-OMD. The results indicated that the absorption of L-dopa was fast with the time to the peak within 30 min, but the formation of 3-OMD was slow with the time to the peak of 120-180 min after IM administration. The IM bioavailability of L-dopa was in the range of 0.70-1.21, and the relative ratios of the formation of 3-OMD at different doses of L-dopa were in the range of 0.79-1.24. No statistically significant difference could be observed for IM bioavailability of L-dopa or for the relative ratios of the formation of 3-OMD in this dose range. The elimination half-lives of L-dopa and 3-OMD also exhibited no significant differences for each dose after IM administration. In addition, both the area under the curve (AUC) and maximum plasma concentration (Cmax) values of L-dopa and 3-OMD increased proportionally over the dose range of 2/0.5-10/2.5 mg/kg for L-dopa/carbidopa, suggesting that L-dopa and 3-OMD obeyed dose-independent pharmacokinetics.
    Relation: Journal of Food and Drug Analysis.(16):21-27.
    Data Type: article
    Appears in Collections:[School of Pharmacy] Periodical Article

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