Alpízar Melchor, de Jesús Reséndiz José, García Martínez Elisa, Dwivedi Sanyog, Trejo Miguel Alejandro
Specialized Centre for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC) & Bioequivalence Studies (E-BIOS-CEDOPEC), Mexico City 11650, Mexico.
Pharmaceutics. 2024 Aug 6;16(8):1044. doi: 10.3390/pharmaceutics16081044.
Enterohepatic circulation (EHC) is a complex process where drugs undergo secretion and reabsorption from the intestinal lumen multiple times, resulting in pharmacokinetic profiles with multiple peaks. The impact of EHC on area under the curve (AUC) has been a topic of extensive debate, questioning the suitability of conventional AUC estimation methods. Moreover, a universal model for accurately estimating AUC in EHC scenarios is lacking. To address this gap, we conducted a simulation study evaluating five empirical models under various sampling strategies to assess their performance in AUC estimation. Our results identify the most suitable model for EHC scenarios and underscore the critical role of meal-based sampling strategies in accurate AUC estimation. Additionally, we demonstrate that while the trapezoidal method performs comparably to other models with a large number of samples, alternative models are essential when sample numbers are limited. These findings not only illuminate how EHC influences AUC but also pave the way for the application of empirical models in real-world drug studies.
肠肝循环（EHC）是一个复杂的过程，在此过程中药物多次经历从肠腔的分泌和重吸收，导致药代动力学曲线出现多个峰值。肠肝循环对曲线下面积（AUC）的影响一直是广泛争论的话题，这对传统AUC估计方法的适用性提出了质疑。此外，缺乏一种在肠肝循环情况下准确估计AUC的通用模型。为了填补这一空白，我们进行了一项模拟研究，评估了在各种采样策略下的五个经验模型，以评估它们在AUC估计中的性能。我们的结果确定了最适合肠肝循环情况的模型，并强调了基于进餐的采样策略在准确AUC估计中的关键作用。此外，我们证明，虽然梯形法在样本数量较多时与其他模型表现相当，但当样本数量有限时，替代模型至关重要。这些发现不仅阐明了肠肝循环如何影响AUC，也为经验模型在实际药物研究中的应用铺平了道路。
