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Rational Approach to the Clinical Protocol Design for Drug Combinations: A Review

並列摘要


Based on the median-effect equation of Chou and the combination index (CI) equation of ChouTalalay, a computer software for automated dose-effect analysis has been developed. This method provides quantitation of synergism (CI<1) and antagonism (CI>1) at different dose and effect levels. Therefore, it allows the selection of the best pair (or triplet) of combination, optimal combination ratio, and the best schedule of treatment. These analyses has been shown to be useful for the clinical protocol design. (Chang et al. Cancer Res. 45: 2434-243 9, 1985). The user-friendly computer pro gram also gives dose-reduction index (DRI) which determines how many fold of dose-reduction is allowed for each drug in synergistic combinations. Dose reduction leads to reduced toxicity while maintaining the desired efficacy (Chou et al. Encyclopedia of Human Biology 2:675-683, 1997 Encyclopedia of Cancer 1.368-379, 1997). The Chou-Talalay method distincts from all. other methods by the fact that it not only takes into account the ”potency” but also the ”shape” of dose-effect curves of each drug and their combinations (Chou & Hayball, CalcuSyn for Windows, Biosoft, Cambridge UK, 1996). This method has been applied in combination of anticancer agents, anti-HIV agents, purging leukemic cells for autologous bone marrow transplantation (Chang et al. Cancer Res. 47:119-122, 1987) and combination of immunosuppressants for organs transplants. Specific examples of the theoretical equations, the median-effect plot, the CI plot, the isobologram, and the polygonogram are illustrated.

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陳宏彰(2010)。薏仁麩皮調節過敏免疫反應之研究及其活性成分之分離與鑑定〔博士論文,國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2010.00077

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