Wilson J M, Slattery J T
J Pharm Sci. 1983 Oct;72(10):1174-8. doi: 10.1002/jps.2600721017.
A method for predicting the maintenance dose of parent drug required to give a desired steady-state concentration of metabolite, using a single determination of metabolite concentration in serum following the first dose of parent drug, is described. Clinical evidence that such a method is feasible for the drug-metabolite pair imipramine-desipramine has been reported. The error inherent in an estimation of maintenance dose based on a single determination of metabolite concentration is a function of sampling time and the first-order elimination rate constants for parent drug and metabolite (K and km, respectively). The method is applicable to drug-metabolite pairs in general by selecting the sampling time (t*) to give minimum error: t* equal 1/km + 1.3/K, when km less than or equal to K, and t* equal 1/K + 1.3/km, when km greater than K (bars denote population mean value). The error expected to be encountered in the application of the method to specific drug-metabolite pairs can be analyzed by the graphical methods described.
本文描述了一种预测母体药物维持剂量的方法，该剂量需使代谢物达到所需的稳态浓度，方法是在给予母体药物首剂后单次测定血清中的代谢物浓度。已有报道表明，对于药物-代谢物对丙咪嗪-去甲丙咪嗪，该方法是可行的临床证据。基于单次代谢物浓度测定来估计维持剂量时固有的误差是采样时间以及母体药物和代谢物的一级消除速率常数（分别为K和km）的函数。通过选择采样时间（t*）以使误差最小，该方法通常适用于药物-代谢物对：当km小于或等于K时，t等于1/km + 1.3/K；当km大于K时，t等于1/K + 1.3/km（横线表示总体均值）。应用该方法于特定药物-代谢物对时预期会遇到的误差可通过所描述的图形方法进行分析。
