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• W2023994142 abstract "The objective of this study was to elucidate the role of P-glycoprotein (P-gp) in restricting the intestinal mucosal permeation of cyclic prodrugs (AOA-DADLE, CA-DADLE, and OMCA-DADLE) of the opioid peptide DADLE (H-Tyr-D-Ala-Gly-Phe-D-Leu-OH). In the Caco-2 cell model, the high Papp,BL-to-AP/Papp,AP-to-BL ratios of AOA-DADLE, CA-DADLE, and OMCA-DADLE (71–117) were significantly decreased by including known P-gp inhibitors, GF-12098, cyclosporine (CyA), or PSC-833, in the incubation media, suggesting that P-gp is restricting the AP-to-BL permeation of these cyclic prodrugs. In the in situ perfused rat ileum model, AOA-DADLE, CA-DADLE, and OMCA-DADLE were shown to exhibit very low permeation into the mesenteric blood (PB=0.40, 0.56 and 0.42×10−7 cm/s, respectively). PSC-833 was found to increase significantly the PB values for all three prodrugs. In contrast, CyA and GF-12918 were either inactive or substantially less active than PSC-833 in increasing the PB values of these prodrugs. These data suggest that, while P-gp plays a role, other factors (e.g., substrate activity for other efflux transporters and/or for metabolic enzymes) may contribute to restricting the permeation of AOA-DADLE, CA-DADLE, and OMCA-DADLE across the rat intestinal mucosa." @default.
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• W2023994142 date "2009-01-01" @default.
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• W2023994142 title "Factors that restrict the intestinal cell permeation of cyclic prodrugs of an opioid peptide (DADLE): Part I. Role of efflux transporters in the intestinal mucosa" @default.
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• W2023994142 doi "https://doi.org/10.1002/jps.21428" @default.
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