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

Rene Holm; Janne Z. Hesselkilde; Erling B. Jørgensen; Anette Müllertz

doi:10.1016/j.ejps.2012.06.007

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

Rene Holm, Janne Z. Hesselkilde, Erling B. Jørgensen, Anette Müllertz

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.

Originalsprog	Engelsk
Tidsskrift	European Journal of Pharmaceutical Sciences
Vol/bind	47
Sider (fra-til)	347-351
ISSN	0928-0987
DOI	https://doi.org/10.1016/j.ejps.2012.06.007
Status	Udgivet - 29 sep. 2012

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title = "Using resin to generate a non-invasive intestinal bile-depleted rat model was unsuccessful",

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.",

keywords = "Former Faculty of Pharmaceutical Sciences",

author = "Rene Holm and Hesselkilde, {Janne Z.} and J{\o}rgensen, {Erling B.} and Anette M{\"u}llertz",

year = "2012",

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doi = "10.1016/j.ejps.2012.06.007",

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T1 - Using resin to generate a non-invasive intestinal bile-depleted rat model was unsuccessful

AU - Holm, Rene

AU - Hesselkilde, Janne Z.

AU - Jørgensen, Erling B.

AU - Müllertz, Anette

PY - 2012/9/29

Y1 - 2012/9/29

N2 - 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.

AB - 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.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.ejps.2012.06.007

DO - 10.1016/j.ejps.2012.06.007

M3 - Journal article

C2 - 22732256

SN - 0928-0987

VL - 47

SP - 347

EP - 351

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

ER -

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

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