Wagner J G
Ther Drug Monit. 1985;7(4):377-86. doi: 10.1097/00007691-198512000-00003.
It has been found empirically that either average or minimum steady-state plasma concentrations (Css) of drugs obeying Michaelis-Menten elimination kinetics give essentially linear plots on semilogarithmic graph paper when Css is plotted versus the maintenance dose (D) or dose rate (R). The equations of such straight lines may be converted to the following nonlinear equation: Css = abD which fits the Css,D data essentially as well as D = VmCss/(Km + Css). The parameter b is analogous to unity plus the interest fraction in logarithmic growth or compound interest calculations, and each drug appears to have a characteristic value of this parameter, with extremely small intersubject variation. From the above equation the following equation, Dn+1 = Dn + 1n(Cn+1/Cn)1n b can be derived, which forms the basis of predicting the needed dosage, Dn+1, to obtain a desired steady-state concentration, Cn+1, using one initial steady-state concentration, Cn, obtained with dose, Dn, and using a population value of b for the drug. It appears that it is the value of the "initial capital" (i.e., a in relation to the initial dose) rather than the "interest fraction" (i.e., b - 1) that causes most of the intersubject variation in Css of a given drug. Several drugs illustrate the usefulness of the method. A semilogarithmic plot also appears to be an excellent method to distinguish simple Michaelis-Menten kinetics from parallel Michaelis-Menten and first order elimination kinetics and from simple first order kinetics with steady-state data in the range 0.3-3 Km.
根据经验发现,对于遵循米氏消除动力学的药物,当稳态血浆浓度(Css)与维持剂量(D)或剂量率(R)作图时,平均或最小稳态血浆浓度在半对数坐标纸上基本呈线性关系。这些直线方程可转换为以下非线性方程:Css = abD,该方程对Css与D数据的拟合效果与D = VmCss/(Km + Css)基本相同。参数b类似于对数增长或复利计算中的1加上利息分数,每种药物似乎都有该参数的特征值,个体间差异极小。由上述方程可推导出以下方程:Dn+1 = Dn + 1n(Cn+1/Cn)1n b,该方程构成了使用一个初始稳态浓度Cn(由剂量Dn获得)以及该药物的群体b值来预测获得所需稳态浓度Cn+1所需剂量Dn+1的基础。似乎导致给定药物Css个体间差异的主要是“初始资本”的值(即与初始剂量相关的a),而非“利息分数”(即b - 1)。几种药物说明了该方法的实用性。半对数图似乎也是区分简单米氏动力学与平行米氏动力学和一级消除动力学以及与0.3 - 3 Km范围内稳态数据的简单一级动力学的绝佳方法。