Schwade J G, Makuch R W, Strong J M, Glatstein E
Cancer Treat Rep. 1982 Sep;66(9):1743-50.
Using pharmacokinetics determined for 27 patients who received iv misonidazole, we have studied the relationship between various pharmacokinetic parameters and the probability of observing peripheral neuropathy. By plotting the probability of observing peripheral neuropathy as a function of each individual parameter and using a linear logistic regression model, we have found a general sigmoid response relating the observations of peripheral neuropathy to the area under the pharmacokinetic curve (AUC), the total cumulative dose throughout the course, the plasma concentration, the plasma elimination half-life, and the total cumulative AUC. By using linear logistic regression analysis, the best correlation with observing peripheral neuropathy was seen with the AUC. Statistical considerations are discussed in depth. This type of analysis may well prove useful for other toxic agents used in cancer treatment.
利用对27名接受静脉注射米索硝唑患者测定的药代动力学数据，我们研究了各种药代动力学参数与观察到周围神经病变的概率之间的关系。通过将观察到周围神经病变的概率作为每个单独参数的函数进行绘图，并使用线性逻辑回归模型，我们发现了一种将周围神经病变的观察结果与药代动力学曲线下面积（AUC）、整个疗程的总累积剂量、血浆浓度、血浆消除半衰期以及总累积AUC相关联的一般S形反应。通过线性逻辑回归分析，发现与观察到周围神经病变相关性最佳的是AUC。深入讨论了统计学考量。这种类型的分析很可能被证明对癌症治疗中使用的其他毒性药物有用。
