Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates

Run Tian, Noriko Koyabu, Hitomi Takanaga, Hirotami Matsuo, Hisakazu Ohtani, Yasufumi Sawada

Research output: Contribution to journalArticle

91 Citations (Scopus)

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 languageEnglish
Pages (from-to)802-809
Number of pages8
JournalPharmaceutical Research
Volume19
Issue number6
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Citrus paradisi
P-Glycoprotein
fexofenadine
Substrates
Jejunum
Ileum
Saquinavir
Small Intestine
Rats
Erythromycin
Verapamil
Intestines
Biological Availability
Western Blotting

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 journalArticle

Tian, Run ; Koyabu, Noriko ; Takanaga, Hitomi ; Matsuo, Hirotami ; Ohtani, Hisakazu ; Sawada, Yasufumi. / Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates. In: Pharmaceutical Research. 2002 ; Vol. 19, No. 6. pp. 802-809.
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AU - Ohtani, Hisakazu

AU - Sawada, Yasufumi

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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.

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