PHARMACODYNAMICS OF CHEMOTHERAPEUTIC EFFECTS - DOSE-TIME-RESPONSE RELATIONSHIPS FOR PHASE-NONSPECIFIC AGENTS
PHARMACODYNAMICS OF CHEMOTHERAPEUTIC EFFECTS - DOSE-TIME-RESPONSE RELATIONSHIPS FOR PHASE-NONSPECIFIC AGENTS
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DOI：
10.1002/jps.2600600618
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发表时间：
1971-01-01
影响因子：
3.8
通讯作者：
JUSKO, WJ
中科院分区：
文献类型：
--
作者：
JUSKO, WJ
开发了药效学关系，以表征与细胞受体不可逆结合的非时相特异性化疗药物的坏死效应。药物作用部位被认为是特定的身体隔室，药物对靶细胞的灭活是由双分子药物-受体相互作用引起的。细胞的周转被认为是通过自然合成和降解过程发生的。基于这些前提，形成对数线性关系，以将存活细胞分数与药理学中心的药物水平-时间积分相关联。当评价整个药物水平-时间过程时，显示积分与剂量成比例，与给药方式无关。来自环磷酰胺对小鼠三个细胞系统的影响的文献的数据证明了方程的有用性和某些治疗意义。
Pharmacodynamic relationships were developed to characterize the necrobiotic effects of phase‐nonspecific chemotherapeutic agents which attach irreversibly to cell receptors. The site of drug action is considered to be a specific body compartment, and target cell inactivation by the agent results from a bimolecular drug‐receptor interaction. Turnover of cells is assumed to occur by natural synthetic and degradative processes. Based on these premises, a log‐linear relationship was evolved to relate the fraction of surviving cells to the drug level‐time integral at the pharmacologic site. The integral was shown to be proportional to the dose and independent of the mode of administration when the entire drug level‐time course is evaluated. Data from the literature for the effects of cyclophosphamide on three cell systems of mice demonstrate the usefulness and certain therapeutic implications of the equations.