Intestinal Epithelium and Drug Transporters

This chapter focuses on factors influencing regional epithelial permeation of drugs related especially to transporters. It highlights the important key messages as regard to modified-release formulations. Drug absorption for ionizable drugs is determined by the pH in the region of intended release. Uptake and efflux transporters expressed in the gastrointestinal tract modulate the absorption of several drugs. Uptake transporters are more likely to act in synergy with other enzymes whose regional distribution is similar to CYP3A4, such as glucuronosyltransferases, sulfotransferases, and glutathione-S-transferases. The impact of the interplay between drug transport and metabolism on regional absorption can also be studied with perfusion techniques using cannulated in situ or isolated ex vivo intestinal regions in the rat. Drug–drug interactions can lead to changed systemic exposure, resulting in variations in drug response of the coadministered drug/s as well as safety concerns especially for low therapeutic index drugs.