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Title: Excipients enhance intestinal absorption of ganciclovir by P-gp inhibition : assessed in vitro by everted gut sac and in situ by improved intestinal perfusion
Authors: Li, Ming
Si, Luqin
Pan, Hongping
Rabba, Abdullah K.
Yan, Fang
Qiu, Jun
Li, Gao
Keywords: Excipients
Ganciclovir - Absorption and adsorption
Intestinal absorption
P-glycoprotein - Absorption and adsorption
Perfusion (Physiology)
Issue Date: 2011
Abstract: In rats we examined the effects of some common excipients on the intestinal absorption of ganciclovir (GCV), a BCS-III drug and substrate of P-gp, by assessing its in vitro transfer from mucosa to serosa and in situ transepithelial permeation. In vitro, all selected excipients (concentration range 0.1–1% [w/v]) could increase the transport amount of GCV in the everted gut sac model. Whereas enhancement by F-68 demonstrated regional differences like verapamil, PEG-400, Tween-80 and EL-35 exhibited no regional differences. In situ studies were performed by an improved perfusion model, single-pass perfusion with whole small intestine, to determine more accurately the permeability of lipophobic compounds. The permeability of GCV was significantly increased by all excipients. The effects of EL-35 and F-68 were dose-dependent but those of PEG-400 and Tween-80 were not. The results suggest that enhancements of intestinal absorption of GCV by these excipients are probably due to inhibition of P-gp mediated drug efflux. It could be deduced from their different properties that both blocking binding sites of P-gp and altering membrane fluidity were involved in their P-gp-inhibition. The former mechanism might be involved for F-68, while the latter one might account for the effects of PEG-400, Tween-80 and EL-35.
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