Using resin to generate a non-invasive intestinal bile-depleted rat model was unsuccessful.
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.
Preformulation, H.Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. rhol@lundbeck.com
René
R
Holm
Janne Z
JZ
Hesselkilde
Erling B
EB
Jørgensen
Anette
A
Müllertz
D000818:Animals; D001646:Bile / Q000378:metabolism; D002792:Cholestyramine Resin / Q000008:administration & dosage*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011136:Polysorbates / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010616:Phenanthrenes; D011136:Polysorbates; D002792:Cholestyramine Resin; D011092:Polyethylene Glycols; C023768:halofantrine