| Summary: | Drug absorption across viable porcine intestines was investigated using an Ussing chamber system. The apparent permeability coefficients, <i>P<sub>app,pig</sub></i>, were compared to the permeability coefficients determined in humans in vivo, <i>P<sub>eff,human</sub></i>. Eleven drugs from the different Biopharmaceutical Classification System (BCS) categories absorbed by passive diffusion with published <i>P<sub>eff,human</sub></i> values were used to test the system. The initial experiments measured <i>P<sub>app,pig</sub></i> for each drug after application in a Krebs–Bicarbonate Ringer (KBR) buffer and in biorelevant media FaSSIF V2 and FeSSIF V2, mimicking fasted and fed states. Strong sigmoidal correlations were observed between <i>P<sub>eff,human</sub></i> and <i>P<sub>app,pig</sub></i>. Differences in the segmental <i>P<sub>app,pig</sub></i> of antipyrine, cimetidine and metoprolol confirmed the discrimination between drug uptake in the duodenum, jejunum and ileum (and colon); the results were in good agreement with human data in vivo. The presence of the P-gp inhibitor verapamil significantly increased <i>P<sub>app,pig</sub></i> across the ileum of the P-gp substrates cimetidine and ranitidine (<i>p</i> < 0.05). Clotrimazole, a potent CYP3A4 inhibitor, significantly increased <i>P<sub>app,pig</sub></i> of the CYP3A4 substrates midazolam, verapamil and tamoxifen and significantly decreased the formation of their main metabolites. In conclusion, the results showed that this is a robust technique to predict passive drug permeability under fasted and fed states, to identify regional differences in drug permeability and to demonstrate the activity of P-gp and CYP3A4.
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