Abstract

The aim of this study was to establish the in situ single-pass intestinal perfusion method in rats for intestinal permeability investigation of drug. Effective permeability coefficients (P_eff) of 15 model drugs were investigated in rat jejunal. Krebs-Ringer buffer solution containing drug was perfused at flow rate of 0.2 ml/min and samples were taken from outlet up to 110 min, steady state was achieved after 30 min perfusion without samples taken. Gravimetric method was used to correct the net water flux. Drug concentrations in perfusion samples were determined using high-performance liquid chromatography-ultraviolet method and P_eff were calculated. The P_eff values obtained by in situ single-pass intestinal perfusion ranged from 0.0146±0.0026×10^-4 cm/s of enalaprilat to 1.77±0.34×10^-4 cm/s of antipyrine. Among the selected model drugs, the P_eff values of high permeability drugs were higher than 0.2×10^-4 cm/s, and less than 0.03×10^-4 cm/s for low permeability drugs. The experimental rat P_eff was highly correlated to the literature human P_eff with correlation coefficient (R²) of 0.99. The observed experimental rat P_eff values were highly correlated to the literature human F_abs (R²=0.93). All investigated model drugs have similar permeability classification compare with literature permeability classification. The predicted human F_abs were linearly correlated with literature human F_abs (R²=0.90). This method could be used for investigation of the intestinal absorption of new compounds, and for prediction the absorption fraction in human. Besides, investigation of the permeability classification of generic drug by in situ single-pass intestinal perfusion can be used for application of biowaiver for industry.