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- W1980996827 abstract "Caco-2 monolayers were used to determine whether verapamil enhanced the transport of hydrophilic compounds across epithelial cells. Transepithelial electrical resistance (TEER) measurements, as an indicator of the opening of tight junctions, and transport experiments with fluorescein-Na (Flu) and FITC-dextran Mw 4000 (FD-4) were used to assess the effect. (+/-) Verapamil concentrations up to 3 x 10(-4) M increased TEER dose-dependently, whereas from concentrations of 7 x 10(-4) M onwards a dose-dependent drop was found. After removal of verapamil (< 10(-3) M) the effects on TEER were reversible within 30 min. A second administration of verapamil after different time intervals produced a much larger effect on TEER than the first administration. The separate R- and S-enantiomers did not reveal a difference in enantiomer effect. (+/-) Verapamil at 7 x 10(-4) M increased Flu transport about 13-fold and 26-fold after the first and second treatment in the same monolayers, respectively. Transport of FD-4 increased approximately 4-fold and 6-fold after the first and second treatment, respectively. Potential damaging effects were assessed by trypan blue exclusion (cell death) and cell detachment. No cell death occurred at verapamil concentrations of 8.5 x 10(-4) M or lower, whereas cell detachment did not occur within 1 hr at all concentrations used in these experiments. At later times detachment was observed at concentrations of 7 x 10(-4) M and higher. Confocal laser scanning microscopy showed that verapamil opens the paracellular route, thereby enhancing the permeability of hydrophilic compounds. However, relatively high concentrations are needed to achieve this effect and only a narrow concentration range can be used without cytotoxic effects, which limits the potential application of verapamil as an absorption enhancing agent." @default.
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- W1980996827 date "1994-09-01" @default.
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- W1980996827 title "Absorption enhancement of hydrophilic compounds by verapamil in Caco-2 cell monolayers" @default.
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- W1980996827 doi "https://doi.org/10.1016/0006-2952(94)90157-0" @default.
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