Yalkowsky S H, Johnson J L H, Sanghvi T, Machatha S G
Pharmaceutical Science, University of Arizona, 1703 E. Mabel St., Tucson, Arizona 85721, USA.
Pharm Res. 2006 Oct;23(10):2475-81. doi: 10.1007/s11095-006-9000-y. Epub 2006 Aug 24.
The ability to predict the passive intestinal absorption of organic compounds can be a valuable tool in drug design. Although Lipinski's 'rule of 5' is commonly used for this purpose, it does not routinely give reliable results. An alternative 'rule of unity' is proposed to predict the absorption efficiency of orally administered drugs that are passively transported. The rule of unity based upon the theoretical principals that govern passive transport. The 'rule of 5' and the 'rule of unity' are compared using experimentally determined passive human intestinal absorption data for 155 drugs. Absorption values which are >50% of the dose are classified as well absorbed and absorption values which are </=50% of the dose are classified as classified as poorly absorbed. Comparison of the two models using a receiver operating characteristic (ROC) plot and McNemar's test reveal striking differences in absorption predictability. The 'rule of 5' gives twice as many false predictions than the 'rule of unity.'
预测有机化合物的被动肠道吸收能力在药物设计中可能是一个有价值的工具。尽管Lipinski的“五规则”通常用于此目的，但它并不能常规地给出可靠的结果。本文提出了一种替代的“统一规则”来预测被动转运的口服给药药物的吸收效率。统一规则基于支配被动转运的理论原理。使用155种药物的实验测定的被动人体肠道吸收数据对“五规则”和“统一规则”进行了比较。吸收值大于剂量50%的药物被归类为吸收良好，吸收值小于或等于剂量50%的药物被归类为吸收不良。使用受试者工作特征（ROC）曲线和McNemar检验对两种模型进行比较，结果显示在吸收预测性方面存在显著差异。“五规则”给出的错误预测比“统一规则”多一倍。
