Department of Engineering, Pharmacy Section, Miguel Hernandez University, Alicante, Spain; Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain.
Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Int J Pharm. 2015 Mar 1;480(1-2):1-7. doi: 10.1016/j.ijpharm.2015.01.014. Epub 2015 Jan 13.
Intestinal drug permeability has been recognized as a critical determinant of the fraction dose absorbed, with direct influence on bioavailability, bioequivalence and biowaiver. The purpose of this research was to compare intestinal permeability values obtained by two different intestinal rat perfusion methods: the single-pass intestinal perfusion (SPIP) model and the Doluisio (closed-loop) rat perfusion method. A list of 15 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was constructed. We assessed the rat intestinal permeability of these 15 model drugs in both SPIP and the Doluisio methods, and evaluated the correlation between them. We then evaluated the ability of each of these methods to predict the fraction dose absorbed (Fabs) in humans, and to assign the correct BCS permeability class membership. Excellent correlation was obtained between the two experimental methods (r(2)=0.93). An excellent correlation was also shown between literature Fabs values and the predictions made by both rat perfusion techniques. Similar BCS permeability class membership was designated by literature data and by both SPIP and Doluisio methods for all compounds. In conclusion, the SPIP model and the Doluisio (closed-loop) rat perfusion method are both equally useful for obtaining intestinal permeability values that can be used for Fabs prediction and BCS classification.
肠道药物渗透率被认为是影响吸收分数的关键决定因素，直接影响生物利用度、生物等效性和生物豁免。本研究旨在比较两种不同的大鼠肠灌流方法：单次肠灌流（SPIP）模型和 Doluisio（闭环）大鼠灌流方法获得的肠道渗透率值。构建了一个具有不同渗透特性（低、中、高，以及被动和主动吸收）的 15 种模型药物的清单。我们评估了这 15 种模型药物在 SPIP 和 Doluisio 方法中的大鼠肠道通透性，并评估了它们之间的相关性。然后，我们评估了这两种方法各自预测人体吸收分数（Fabs）的能力，并确定正确的 BCS 渗透性分类。两种实验方法之间得到了极好的相关性（r（2）=0.93）。文献中的 Fabs 值与两种大鼠灌注技术的预测值之间也显示出极好的相关性。根据文献数据以及 SPIP 和 Doluisio 方法，所有化合物的 BCS 渗透性分类都相同。总之，SPIP 模型和 Doluisio（闭环）大鼠灌流方法在获得可用于 Fabs 预测和 BCS 分类的肠道渗透率值方面同样有用。
