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Sturm, K. et al.

Sturm, Levstik, Demopoulos, Kristl,

Permeability characteristics of novel aldose reductase inhibitors using rat jejunum in vitro.

The aim of this study was to estimate in vivo permeability and bioavailability of epalrestat and newly synthesized compounds with possible therapeutic activity as aldose enzyme inhibitors (ARIs). For this purpose permeability in vitro using rat jejunum mounted in side-by-side diffusion cells was determined. Tested substances were found to be low and moderately permeable and some of them were also substrates for efflux transporters. It was shown, that the higher efflux for some derivatives was due to MRP-2, but not Pgp involvement. Tested ARIs do not share the same efflux transporter with epalrestat, the only ARI currently on the market in Japan. The most permeable compound, a 2,6-difluoro-4-pyrrol-1ylphenol derivative, is not a substrate for efflux transporters and would therefore be the most promising lead compound for further investigation of potent ARIs.[1]

References

Permeability characteristics of novel aldose reductase inhibitors using rat jejunum in vitro. Sturm, K., Levstik, L., Demopoulos, V.J., Kristl, A. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. (2006) [Pubmed]

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