Numerous in vitro methods have been used in the drug selection process for assessing the intestinal absorption potential of drug candidates. In vitro techniques for assessment of permeability are less labor and cost intensive compared to in vivo animal studies. One universal issue with all the in vitro systems is that the effect of physiological factors such as gastric emptying rate, gastrointestinal transit rate, gastrointestinal pH, etc. cannot be incorporated in the data interpretation.
Each in vitro method has its distinct advantages and drawbacks. Based on the specific goal, one or more of these methods can be used as a screening tool for selecting compounds during the drug discovery process. The successful application of in vitro models to predict drug absorption across the intestinal mucosa depends on how closely the in vitro model mimics the characteristics of the in vivo intestinal epithelium. Although it is very difficult to develop a single in vitro system that can simulate all the conditions existing in the human intestine, various in vitro systems are used routinely as decision making tools in early drug discovery.
It is extremely difficult to obtain viable human tissues for permeability studies on a regular basis. Since animal intestinal tissues are also made up of essentially the same kind of endothelial cells, permeability screening for drug discovery purposes is routinely carried out using various animal species. Excised animal tissue models have been used since the 1950s to explore the mechanism of absorption of nutrients from the intestine. Evidence on the uptake of glucose against a concentration gradient (Quastel, 1961) provided impetus for mechanistic studies involving excised tissues from the intestine of animals. However, the viability of the excised tissues is difficult to maintain since the tissues are devoid of direct blood supply and need constant oxygenation. Some of the more widely used methods for absorption and permeability studies are described below.
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