Colburn W A, Lucek R W
Pharmacokinetics/Drug Metabolism, Warner-Lambert/Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105.
Biopharm Drug Dispos. 1988 Sep-Oct;9(5):465-75. doi: 10.1002/bod.2510090505.
Drugs that are involved in the enterohepatic circulation (EHC) generally exhibit complex disposition profiles and are difficult to describe by classical methods. A noncompartmental method for calculating the area under the curve from time zero to time infinity (AUC) for substances that are involved the EHC is developed and tested. Previous methods have been based on specific compartmental models and/or have been limited to a single enterohepatic cycle. The current method uses the following equations: (formula; see text) for an IV dose or (formula; see text) for an oral dose where kaR is the apparent first-order absorption rate constant and beta R is the rate constant that describes the decline in blood concentrations of drug at 24-h intervals, i.e., 12, 36, and 60 or 24, 48, and 72 h, etc. AUC0-24 can be calculated by trapezoidal summation. The precision of this method is dependent on the number of observations during the 0-24 h sampling period as well as the accuracy of kaR and beta R. For drugs that are subject to a distinct distribution phase(s), error can be introduced into the AUC0-infinity value if pseudo-equilibrium has not been achieved during the first 24-hour interval. Although the method depends on a linearization process, it is truly concompartmental ('model-independent') in nature.
参与肠肝循环（EHC）的药物通常具有复杂的处置过程，难以用传统方法描述。本文开发并测试了一种用于计算参与EHC的物质从零时间到无穷时间曲线下面积（AUC）的非房室方法。以前的方法基于特定的房室模型和/或仅限于单个肠肝循环。当前方法使用以下公式：静脉注射剂量时为（公式；见原文），口服剂量时为（公式；见原文），其中kaR是表观一级吸收速率常数，βR是描述药物血药浓度在24小时间隔（即12、36和60小时或24、48和72小时等）下降的速率常数。AUC0-24可通过梯形求和计算。该方法的精度取决于0-24小时采样期内的观察次数以及kaR和βR的准确性。对于具有明显分布相的药物，如果在第一个24小时间隔内未达到伪平衡，则可能会将误差引入AUC0-无穷大值。尽管该方法依赖于线性化过程，但本质上它是真正的非房室（“与模型无关”）方法。
