Investigation of Apparent Oil/Water Partition Coefficients of Berberine and Its Absorption Characteristics in in situ Intestinal Perfusion Model

Abstract:

Objective: To determine apparent oil-water partition coefficient of berberine monomer and berberine in coptis total alkaloids,investigate absorption kinetics of berberine at jejunum and ileum of rats from berberine monomer and coptis total alkaloids and Qingre Tongfu tablets,then compare correlation between apparent oil-water partition coefficient and absorption kinetics. Method: Apparent octanol-water partition coefficient of berberine was determined by shake-flask method,in situ intestinal recirculating perfusion model of berberine was performed to study its absorption at different intestinal regions.The concentrations of berberine were analyzed by UPLC.Calculated berberine intestinal absorption rate constant(Ka) and apparent permeability coefficient(P_app) in different intestinal regions of rats. Result: Oil-water partition coefficient of berberine and coptis total alkaloids were 0.213 5 and 0.175 7,respectively.Ka of berberine were 0.046 6 and 0.034 9 in jejunum and ileum,respectively;While P_app were 4.88×10^-6,4.13×10^-6cm·s^-1,respectively.Ka of berberine in coptis total alkaloids were 0.035 1 and 0.026 6 in jejunum and ileum,respectively;While P_app were 3.92×10^-6,3.21×10^-6cm·s^-1,respectively.Ka of berberine in Qingre Tongfu tablets were 0.028 3 and 0.018 1 in jejunum and ileum,respectively;While P_app were 3.11×10^-6and 2.23×10^-6cm·s^-1,respectively(n=6). Conclusion: Berberine had absorption in jejunum and ileum with slow absorption rate,but the former was greated than the latter with a significant difference;Absorption rate of berberine was in order of berberine reference standard>coptis total alkaloids>Qingre Tongfu tablets,the predicted results of oil-water partition coefficient of berberine were basically the same with intestinal absorption results.