Piotrovskiĭ V K
Biofizika. 1991 Sep-Oct;36(5):899-903.
A model-independent method for estimating an elimination rate constant of a metabolite of exogenous substance is suggested as an alternative to known methods. The new method (named the initial slope method) uses blood (plasma) concentration-time data of both the substance and the metabolite obtained after an extravascular impulse input of the substance. The metabolite input is not needed substantially facilitating the experiment. The method is based upon the assessment of areas under the substance and metabolite concentration-time curves, the initial substance concentration, and the initial slope of the metabolite concentration-time curve. The method was tested using artificial data generated on the basis of a compartment model for the substance and metabolite kinetics. It was shown providing nonbiased estimates of a true metabolite elimination rate constant irrespective of the structure of the model used to generate data. Other methods failed to provide such estimates.
提出了一种独立于模型的方法来估计外源性物质代谢物的消除速率常数,作为已知方法的替代方法。新方法(称为初始斜率法)使用物质血管外脉冲输入后获得的物质和代谢物的血液(血浆)浓度-时间数据。基本上不需要代谢物输入,这便于实验。该方法基于对物质和代谢物浓度-时间曲线下面积、初始物质浓度以及代谢物浓度-时间曲线的初始斜率的评估。使用基于物质和代谢物动力学的房室模型生成的人工数据对该方法进行了测试。结果表明,无论用于生成数据的模型结构如何,该方法都能提供真实代谢物消除速率常数的无偏估计。其他方法无法提供这样的估计。