European Journal of Pharmaceutical Sciences 2012-09-29

Using resin to generate a non-invasive intestinal bile-depleted rat model was unsuccessful.

René Holm, Janne Z Hesselkilde, Erling B Jørgensen, Anette Müllertz

Index: Eur. J. Pharm. Sci. 47(2) , 347-51, (2012)

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Abstract

The purpose of this study was to evaluate if a rat model, based upon co-administration of the anion-exchanging resin, cholestyramine, could replace surgery when evaluating the importance of bile on drug absorption. Two different formulations were used for the administration of halofantrine; polyethylene glycol 400 (PEG 400) and PEG 400/polysorbate 80 (50:50, w/w%), as a positive and negative control on the dependency of bile. No significant effect of the resin was detected after evaluation of three different pre-dosing regimes, but in line with previous studies the formulation containing polysorbate 80 showed a significant increase in the absorption of halofantrine. This study therefore demonstrates that the pre-dosing of rats with Cholestyramine can not replace surgical bile duct cannulation if a formulation needs to be evaluated for its bile dependency.Copyright © 2012 Elsevier B.V. All rights reserved.