Zaharko D S, Kelley J A, Tomaszewski J E, Hegedus L, Hartman N R
Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Invest New Drugs. 1991 Feb;9(1):9-17. doi: 10.1007/BF00194539.
A hybrid compartmental-physiological model for cyclopentenyl cytosine (CPE-C) is designed on the basis of early limited rodent pharmacokinetic data. Application of model independent pharmacokinetics and biochemical knowledge was first used to conceptualize such a model. The approach was to scale the physiological parameters of the model (compartmental clearances) and keep constant the anatomic parameters of the model (compartment volumes). Scaling of physiological mechanisms was based on body weight/surface area ratios. Using these principles, simulations with the model can reasonably anticipate the in vivo behavior of (CPE-C) in several species (mouse, rat, dog). The model is useful in understanding species differences in pharmacokinetic behavior of CPE-C.
基于早期有限的啮齿动物药代动力学数据，设计了一种环戊烯基胞嘧啶（CPE-C）的混合房室-生理模型。模型独立药代动力学和生化知识的应用首次被用于构建这样一个模型。方法是按比例缩放模型的生理参数（房室清除率），并保持模型的解剖学参数（房室容积）不变。生理机制的缩放基于体重/表面积比。利用这些原理，该模型的模拟可以合理预测CPE-C在几种物种（小鼠、大鼠、狗）中的体内行为。该模型有助于理解CPE-C药代动力学行为的物种差异。
