Studies on intestinal absorption of sulpiride (2): transepithelial transport of sulpiride across the human intestinal cell line Caco-2.

To determine the transport mechanism of sulpiride in an in vitro model of the human intestine, we investigated the transepithelial transport of this agent in Caco-2 cells. The transepithelial transport and intracellular accumulation of sulpiride were measured using Caco-2 cell monolayers cultured on a permeable membrane. The transepithelial transport of sulpiride in Caco-2 cells showed temperature dependence, and the transport was enhanced at weakly acidic pH on the apical side. These results demonstrate that the transepithelial transport of sulpiride is carrier mediated. To identify the drug transporter species that take part in the transepithelial transport of sulpiride, we examined the effects with the addition and preloading with specific substrates and inhibitors of various drug transporters. The results obtained from these examinations indicated that the apical-to-basolateral transport of sulpiride is mediated by the peptide transporter PEPT1, organic cation transporters OCTN1 and OCTN2 on the apical membrane, and the basolateral peptide transporter on the basolateral membrane. The basolateral-to-apical transport is mediated by the basolateral peptide transporter and organic cation transporter OCT1 on the basolateral membrane and by P-glycoprotein on the apical membrane. A decrease in the absorption of sulpiride may occur in coadministration protocols involving PEPT1-, OCTN1-, and OCTN2-transported drugs. Coadministration using the P-glycoprotein-transported drugs, in contrast, may enhance the absorption of sulpiride.