Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, United States.
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, United States.
Int J Pharm. 2016 Jun 15;506(1-2):110-5. doi: 10.1016/j.ijpharm.2016.04.013. Epub 2016 Apr 8.
High-throughput screening methods have increased the number of poorly water-soluble, highly permeable drug candidates. Many of these candidates have increased bioavailability when administered with food (i.e., exhibit a positive food effect). Food is known to impact drug bioavailability through a variety of mechanisms, including drug solubilization and prolonged gastric residence time. In vitro dissolution media that aim to mimic in vivo gastrointestinal (GI) conditions have been developed to lessen the need for fed human bioequivalence studies. The objective of this work was to develop an in vitro lipolysis model to predict positive food effect of three BCS Class II drugs (i.e., danazol, amiodarone and ivermectin) in previously developed lipolysis media. This in vitro lipolysis model was comparatively benchmarked against FeSSIF and FaSSIF media that were modified for an in vitro lipolysis approach, as FeSSIF and FaSSIF are widely used in in vitro dissolution studies. The in vitro lipolysis model accurately predicted the in vivo positive food effect for three model BCS class II drugs. The in vitro lipolysis model has potential use as a screening test of drug candidates in early development to assess positive food effect.
高通量筛选方法增加了许多水溶性差、渗透性高的候选药物。当这些候选药物与食物一起给药时，许多候选药物的生物利用度会增加（即表现出正的食物效应）。众所周知，食物通过多种机制影响药物的生物利用度，包括药物的溶解和延长胃停留时间。已经开发出旨在模拟体内胃肠道 (GI) 条件的体外溶解介质，以减少对进食人体生物等效性研究的需求。这项工作的目的是开发一种体外脂肪酶模型，以预测三种 BCS 类 II 药物（即丹那唑、胺碘酮和伊维菌素）在先前开发的脂肪酶介质中的正食物效应。该体外脂肪酶模型与 FeSSIF 和 FaSSIF 介质进行了比较，FeSSIF 和 FaSSIF 介质经过修改可用于体外脂肪酶方法，因为 FeSSIF 和 FaSSIF 广泛用于体外溶解研究。该体外脂肪酶模型准确预测了三种模型 BCS 类 II 药物的体内正食物效应。体外脂肪酶模型具有作为早期开发中候选药物筛选测试的潜力，以评估正食物效应。
