Abstract
Transepithelial transport characteristics of diphenhydramine, an antihistamine, were studied in cultured human intestinal Caco-2 cell monolayers. In the apical-to-basolateral transport studies, the flux and cellular accumulation of diphenhydramine were influenced by the apical extracellular pH values. The accumulation and transepithelial transport were saturable and inhibited by chlorpheniramine. In the basolateral-to-apical transport, the accumulation and transport of diphenhydramine were also inhibited by chlorpheniramine. Diphenhydramine accumulation from both sides was stimulated by preloading the cells with chlorpheniramine, indicating the existence of specific transport systems in the both apical and basolateral membranes. Furthermore diphenhydramine was preferentially transported and effluxed to the apical direction. Finally, it was suggested that this transport system recognized tertiary amine compounds having a N-dimethyl or -diethyl residue in their structures. These results suggest that novel pH-dependent transport systems contribute to the intestinal absorption and secretion of tertiary amine compounds such as diphenhydramine.
