Regional Differences in Transport and Metabolism of Drugs

Investigations of regional differences in permeability and metabolism have been performed by using various animal models [22, 29, 75, 102, 109, 112, 137]. Animal tissues, mainly rat specimens, are widely used in the Ussing chamber to investigate transport of drugs across specific regions of the intestine [29, 75, 138], whereas studies in human tissues are few due to the limited availability of tissue specimens. 

We have emphasized the need for more in vivo studies to deconstruct the dynamic interplay between mechanisms of drug transport and metabolism in the human intestine. There is also a need to further develop in vivo techniques to directly measure these processes in various regions along the GI tract in humans and to relate the findings to physiological/pathophysiological conditions. 

This will increase our knowledge of the important transport mechanisms and will provide in vivo data leading to the development and validation of rapid and more reliable in vitro intestinal models. 

1 Amidon, G.L., Lennernas, H., Shah, V.P. and Crison, J.R. (1995) A theoretical basis for a biopharmaceutic drug classification the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical Research, 12, 413-420. 

2 Fromm, M.F., Busse, D., Kroemer, H.K. and Eichelbaum, M. (1996) Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Hepatology, 24, 796-801. 

---