本文選題：多藥合用 + 藥物相互作用　； 參考：《中國藥理學與毒理學雜志》2016年12期

【摘要】：許多嚴重疾病如癌癥的病因復雜,屬于多靶點疾病,針對多個靶點聯(lián)合用藥比單靶點用藥更容易實現(xiàn)治療目的。藥物聯(lián)用可產(chǎn)生多層面的相互作用,最終表現(xiàn)為藥效發(fā)生協(xié)同、相加或拮抗。對其進行定量評價的前提是獲得多藥合用組合的預期相加效應值。但長期以來一直缺乏精確計算協(xié)同、相加和拮抗的可靠方法,使新復方藥物研究等發(fā)展受阻。通過等效劑量兌換和引入藥理學中的藥效的序貫和集合原理,作者發(fā)現(xiàn)了多藥合用組合預期相加效應的數(shù)學規(guī)律,簡述如下:多藥合用劑量組合的預期相加效應值是一個連續(xù)的數(shù)值范圍,即預期相加效應值是藥物組合劑量的閉區(qū)間數(shù)集函數(shù),建立了通用型計算公式。在二維坐標系中顯示為一條量效曲帶,與多藥合用組合的實際量效曲線構成一幅"一條曲帶和一條曲線"的圖像。組成預期相加量效曲帶的量效曲線的數(shù)量,隨著合用藥物數(shù)量的增加呈指數(shù)性增長。通過計算實際量效曲線和相加量效曲帶的交點坐標,能夠得出多藥合用組合藥效發(fā)生協(xié)同、相加或拮抗的劑量范圍;通過比較實際量效曲線中的效應值(或劑量值)與相加量效曲帶的偏離狀況,能夠得出發(fā)生協(xié)同、相加或拮抗程度的指標,如劑量合用指數(shù)和效應合用指數(shù)等。該方法能為新復方藥物研發(fā)、多藥聯(lián)合效應的定量評價和中藥復方的效應評價等提供可靠通用的計算方法,簡稱為"一帶一線"法。
[Abstract]:Many serious diseases such as cancer have complicated etiology and belong to multi-target diseases. A combination of drugs can produce multiple-level interactions that ultimately result in synergistic, additive or antagonistic effects. The premise of quantitative evaluation is to obtain the expected additive effect of multidrug combination. However, for a long time, there is a lack of reliable methods of accurate calculation, addition and antagonism, which impedes the development of new compound drugs. By equivalent dose exchange and the sequential and collective principle of pharmacological efficacy, the authors found the mathematical law of the expected additive effect of multidrug combination. The results are summarized as follows: the expected additive effect of multidrug combination dose combination is a continuous numerical range, that is, the expected additive effect value is a set function of closed interval number of drug combination dose, and a general calculation formula is established. In a two-dimensional coordinate system, a quantitative curved band is displayed, and the actual volume effect curve combined with multiple drugs constitutes an image of "one curved band and one curve". The number of dose-response curves composed of the expected additive effect curve increased exponentially with the increase of the amount of combined drugs. By calculating the coordinate of the intersection point between the actual dose effect curve and the additive effect curve, the dose range of synergistic, additive or antagonistic effect of multi-drug combination can be obtained. By comparing the deviation between the effect value (or dose value) in the actual dose-effect curve and the additive effect curve, the indexes of synergistic, additive or antagonistic degree, such as dose combination index and effect combination index, can be obtained. This method can provide a reliable and general calculation method for the research and development of new compound drugs, quantitative evaluation of multi-drug combination effect and effect evaluation of traditional Chinese medicine compound.
【作者單位】： 軍事醫(yī)學科學院放射與輻射醫(yī)學研究所藥物毒理與腫瘤藥理實驗室;
【分類號】：R96

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