Single-pass intestinal perfusion to establish the intestinal permeability of model drugs in mouse


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Abstract

The aim of the present work was to study the intestinal permeabilities (Peff) of five model drugs: furosemide, piroxicam, naproxen, ranitidine and amoxicillin in the in situ intestinal perfusion technique in mice and compare them with corresponding rat and human in vivo Peff values.The main experimental conditions were: mice CD1 30–35 g, test drug concentrations in perfusion experiments (the highest dose strength dissolved in 250 mL of PBS pH 6.2) and flow rate of 0.2 mL/min. The test compounds were assayed following a validated HPLC method. The effective permeability coefficients at steady-state were calculated after correcting the outlet concentration following the gravimetric correction method proposed by Sutton et al. (2001). The permeability coefficient values ranged from 0.1751 ± 0.0756 × 10−4 cm/s for ranitidine to 17.19 ± 4.16 × 10−4 cm/s for naproxen.The mouse method correctly assigned the BCS permeability classification of a given drug and a correlation between mouse permeability data and the fraction of an oral dose absorbed in humans was achieved (FA = 1 − exp(−34,745·Peff(mouse)); R = 0.9631).Based on the results obtained, we conclude that mouse can be considered a valuable tool in the evaluation of intestinal permeability in order to predict the extent of human gastrointestinal absorption following oral administration of a drug.

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