Abstract
Purpose. 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 rhodamine123 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.
| Original language | English |
|---|---|
| Pages (from-to) | 802-809 |
| Number of pages | 8 |
| Journal | Pharmaceutical Research |
| Volume | 19 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2002 |
| Externally published | Yes |
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Keywords
- Fexofenadine
- Grapefruit juice
- Intestinal efflux
- Orange juice
- P-glycoprotein (P-gp)
- Saquinavir
ASJC Scopus subject areas
- Chemistry(all)
- Pharmaceutical Science
- Pharmacology
Cite this
Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates. / Tian, Run; Koyabu, Noriko; Takanaga, Hitomi; Matsuo, Hirotami; Ohtani, Hisakazu; Sawada, Yasufumi.
In: Pharmaceutical Research, Vol. 19, No. 6, 2002, p. 802-809.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates
AU - Tian, Run
AU - Koyabu, Noriko
AU - Takanaga, Hitomi
AU - Matsuo, Hirotami
AU - Ohtani, Hisakazu
AU - Sawada, Yasufumi
PY - 2002
Y1 - 2002
N2 - Purpose. 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 rhodamine123 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.
AB - Purpose. 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 rhodamine123 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.
KW - Fexofenadine
KW - Grapefruit juice
KW - Intestinal efflux
KW - Orange juice
KW - P-glycoprotein (P-gp)
KW - Saquinavir
UR - http://www.scopus.com/inward/record.url?scp=0036288273&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036288273&partnerID=8YFLogxK
U2 - 10.1023/A:1016100715125
DO - 10.1023/A:1016100715125
M3 - Article
C2 - 12134950
AN - SCOPUS:0036288273
VL - 19
SP - 802
EP - 809
JO - Pharmaceutical Research
JF - Pharmaceutical Research
SN - 0724-8741
IS - 6
ER -