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題 名 | Rational Approach to the Clinical Protocol Design for Drug Combinations: A Review=在臨床治療方案中針對藥物合併療法之合理設計:文獻回顧 |
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作 者 | 張泰琮; 周廷潮; | 書刊名 | 臺灣兒科醫學會雜誌 |
卷 期 | 41:6 民89.11-12 |
頁 次 | 頁294-302 |
分類號 | 418.8 |
關鍵詞 | 藥物合併療法; Quantitative dose effect analysis; Median-effect plot; Drug combination design; Combination index; |
語 文 | 英文(English) |
英文摘要 | 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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