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• W2093775283 startingPage "1334" @default.
• W2093775283 abstract "In the present study, we successfully downscaled, for the first time, the in situ intestinal perfusion technique with mesenteric blood sampling from rat to mouse. To evaluate the feasibility of this approach, we assessed the apparent permeability (<i>P</i>_app) of mouse intestine for a set of marker compounds [atenolol, paracellular transport; metoprolol, transcellular transport; talinolol, P-glycoprotein (P-gp)-mediated efflux] in both wild-type and P-gp-deficient mice. In wild-type mice, the observed <i>P</i>_app values for atenolol (1.8 ± 0.3 × 10^–6 cm/s) and metoprolol (50.2 ± 20.1 × 10^–6 cm/s) were not significantly affected by inclusion of the P-gp inhibitor verapamil. In contrast, the <i>P</i>_app value for talinolol (0.9 ± 0.3 × 10^–6 cm/s) increased 5-fold in the presence of verapamil. The similarity between these values and previously determined <i>P</i>_app values in rats indicates comparable passive barrier functions and P-gp-mediated efflux transport between mice and rats. In comparison with wild-type mice, the apparent permeability in P-gp-deficient <i>mdr1a/1b</i>(–/–) mice was significantly altered for talinolol (7-fold increase) but not for atenolol or metoprolol. Because of the availability of knockout mice, the intestinal perfusion technique with mesenteric blood sampling in mice may become an important tool to elucidate the role of intestinal metabolism and active transport in drug absorption during preclinical drug evaluation." @default.
• W2093775283 created "2016-06-24" @default.
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• W2093775283 date "2009-03-09" @default.
• W2093775283 modified "2023-09-24" @default.
• W2093775283 title "INTESTINAL PERFUSION WITH MESENTERIC BLOOD SAMPLING IN WILD-TYPE AND KNOCKOUT MICE" @default.
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• W2093775283 doi "https://doi.org/10.1124/dmd.109.026591" @default.
• W2093775283 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19273528" @default.
• W2093775283 hasPublicationYear "2009" @default.
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