Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates.
OBJECTIVE
The aim of this study is to investigate the effects of 50% ethyl acetate extracts of grapefruit juice (GFJ) and orange juice (OJ) on the transport activity of P-glycoprotein (P-gp) in the rat small intestine.


METHODS
The efflux of P-gp substrates from rat everted sac in the absence or presence of verapamil, GFJ, OJ or erythromycin was measured. Rhodamine123, fexofenadine and saquinavir were used as P-gp substrates. P-gp expression levels in the rat jejunum and ileum were determined by Western blot analysis.


RESULTS
The efflux of rhodamine123 from the everted sac increased from the apex of the jejunum to the low ileum and the expression of P-gp in the ileum was 2.31-fold higher than that in the jejunum. Verapamil and the 50% GFJ and OJ extracts inhibited the efflux from the intestine of all three drugs tested. Erythromycin decreased the efflux of rhodaminel23 and fexofenadine, but did not affect the efflux of saquinavir in the intestine.


CONCLUSIONS
GFJ and OJ extracts inhibited the efflux of P-gp substrates from the small intestine. Therefore, they may enhance the oral bioavailability of P-gp substrates by increasing absorption in the small intestine.
Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Run
R
Tian
Noriko
N
Koyabu
Hitomi
H
Takanaga
Hirotami
H
Matsuo
Hisakazu
H
Ohtani
Yasufumi
Y
Sawada
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001628:Beverages; D032083:Citrus paradisi / Q000737:chemistry; D032084:Citrus sinensis / Q000737:chemistry; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D020112:Rhodamine 123; D013379:Substrate Specificity / Q000502:physiology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010936:Plant Extracts; D020112:Rhodamine 123