Major active components in grapefruit, orange, and apple juices responsible for OATP2B1-mediated drug interactions.

  title={Major active components in grapefruit, orange, and apple juices responsible for OATP2B1-mediated drug interactions.},
  author={Yoshiyuki Shirasaka and Megumi Shichiri and Takanori Mori and Takeo Nakanishi and Ikumi Tamai},
  journal={Journal of pharmaceutical sciences},
  volume={102 1},
We aimed to explore the major active components in grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ) that are responsible for OATP2B1-mediated drug interactions, by means of in vitro studies using Xenopus oocytes expressing OATP2B1 with a typical OATP2B1 substrate, estrone-3-sulfate. All three juices inhibited OATP2B1-mediated estrone-3-sulfate uptake with half-maximum inhibition (IC(50) ) values of 0.222% (GFJ), 0.807% (OJ), and 2.27% (AJ). Eight major flavonoids (naringin… 
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Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity.
All six furanocoumarins showed stronger CYP3A inhibitory potencies after preincubation in the presence of NADPH, suggesting that both competitive and mechanism-based inhibition occur in a grapefruit juices-drug interaction.
A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction.
Furanocoumarins are the active ingredients in GFJ responsible for enhancing the systemic exposure of felodipine and probably other CYP3A4 substrates that undergo extensive intestinal first-pass metabolism.
Naringin is a Major and Selective Clinical Inhibitor of Organic Anion‐Transporting Polypeptide 1A2 (OATP1A2) in Grapefruit Juice
Naringin most probably directly inhibited enteric OATP1A2 to decrease oral fexofenadine bioavailability and may be the first report of a single dietary constituent clinically modulating drug transport.
Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins.
The effect of grapefruit juice on oral availability of CYP3A4 substrates can be largely accounted for by the presence of 6',7'-dihydroxybergamottin although other furanocoumarins probably also contribute.
Species Difference in the Effect of Grapefruit Juice on Intestinal Absorption of Talinolol between Human and Rat
The present study indicated that the species difference in the effect of GFJ on intestinal absorption of talinolol between humans and rats may be due to differences in the affinity of naringin for OATP/Oatp and MDR1/Mdr1 transporters between the two species.
Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporine.
Furanocoumarins mediate, at least partially, the cyclosporine-GFJ interaction in vivo, and a plausible mechanism involves the combined inhibition of enteric CYP3A4 and P-glycoprotein.
Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice.
Results indicate that BG, the primary furanocoumarin extracted from grapefruit juice, is a mechanism-based inactivator of P450 3A4.
Apple juice greatly reduces systemic exposure to atenolol.
Apple juice markedly reduced systemic exposure to atenolol and the genetic variation of SLCO2B1 c.1457C>T had a minimal effect on the pharmacokinetics of atenorol when the drug was administered with water or apple juice.
Differential effect of grapefruit juice on intestinal absorption of statins due to inhibition of organic anion transporting polypeptide and/or P-glycoprotein.
Oatp and/or P-gp contribute to the intestinal absorption of statins, and the differential effect of GFJ on pravastatin and pitavastatin absorption is at least partly accounted for by the different inhibitory effects of naringin on these transporters.
Polyphenols are intensively metabolized in the human gastrointestinal tract after apple juice consumption.
The gastrointestinal passage seems to play an important role in the colonic availability of apple polyphenols, and the mean degree of polymerization of the procyanidins varied depending on the time point of excretion.