College of Pharmacy, Seoul National University, Seoul, Korea.
Drug Dev Ind Pharm. 2013 Oct;39(10):1515-22. doi: 10.3109/03639045.2012.714787. Epub 2012 Aug 31.
The Biopharmaceutics Classification System (BCS) was developed to facilitate estimation of the in vivo pharmacokinetic performance of drugs from human intestinal permeability and solubility. However, the measurement of human in vivo intestinal permeability, unlike that of solubility, is problematic and inefficient. Thus, rat in vitro intestinal permeability results obtained via the Ussing chamber technique are often used instead. However, these data could be unreliable due to difficulty in maintaining the viability of the dissected intestinal membrane in the Ussing chamber. Therefore, a more efficient method to obtain a reliable in vitro permeability is mandatory. Here, we propose a new approach by introducing a novel factor called the permeability ratio (PR). Basically, PR is a rat in vitro intestinal permeability obtained from the Ussing chamber, which is then corrected by the permeability of lucifer yellow, a paracellular permeability marker. To prove the validity of the method, 12 model drugs representing different BCS classes were tested, and the correlation with human in vivo intestinal permeability was high. More importantly, the new method perfectly classified all 12 model drugs. The results indicate that PR is a reliable factor with high correlation to human in vivo intestinal permeability, which can further be used to accurately predict the BCS classification.
生物药剂学分类系统 (BCS) 的开发旨在促进从人体肠道通透性和溶解度来预测药物的体内药代动力学性能。然而，与溶解度的测量不同，人体体内肠道通透性的测量存在问题且效率低下。因此，通常使用 Ussing 室技术获得的大鼠在体肠渗透性结果来代替。然而，由于在 Ussing 室中难以保持分离的肠膜的活力，这些数据可能不可靠。因此，需要一种更有效的方法来获得可靠的体外渗透性。在这里，我们通过引入一个称为通透性比（PR）的新因子来提出一种新方法。基本上，PR 是从 Ussing 室获得的大鼠在体肠通透性，然后通过作为细胞旁通透性标记物的荧光素黄的通透性进行校正。为了证明该方法的有效性，我们测试了 12 种代表不同 BCS 类别的模型药物，与人体体内肠通透性具有很高的相关性。更重要的是，该新方法可以完美地对所有 12 种模型药物进行分类。结果表明，PR 是与人体体内肠通透性具有高度相关性的可靠因子，可进一步用于准确预测 BCS 分类。
