Experimental models for the investigation of water and solute transport in man. Implications for oral rehydration...

For patients suffering from mild to moderate dehydration, oral rehydration therapy has proved a simple and efficacious treatment. There remains, however, a need to develop improved oral rehydration solutions (ORS), and suitable experimental models are required to develop and assess new formulations. The ideal model for such investigations would take into account rates of gastric emptying, influx and efflux of water and solutes in the intestine, and the consequent changes in body composition. As no such definitive model is currently available, a variety of techniques are used to examine parts of the process of intestinal absorption. Clinical studies which assess the recovery of dehydrated patients during therapy using different ORS will ultimately evaluate the efficacy of treatment. However, ethical considerations, the relative insensitivity of this technique and the exacting nature of such studies make this approach unsuitable for the development of specific ORS. Gastric emptying of solutions can be determined by a variety of techniques, among which the radioactive tracer method offers the advantage of having no direct effect on the emptying rate, giving almost continuous measurement and allowing the use of relatively small volumes of fluids. Perfusion techniques allow measurement of the net flux of water and solute in predetermined sections of the intact human intestine. Measurement of the rate of accumulation in the circulation of orally ingested tracer molecules for water and solutes can estimate unidirectional flux. This method allows for the rates of gastric emptying and intestinal absorption of the test substance, but the rate of efflux of the tracer from the vascular space must be known to calculate net uptake. Each of these models has limitations, and care must be taken in interpreting the results in a clinical context. However, their use in the development of improved formulations is well established.