CAM InteractionsE. DIETARY

Lowering drug blood levels with grapefruit juice: When’s it significant?

Ask about the grapefruit/drug interaction and most people think of the increased blood levels of statins when grapefruit is eaten before taking a dose.

Now, Dr. David Bailey at the University of Western Ontario, in London, Ontario, has reviewed fruit juice interactions that result in lower drug blood levels.

Here’s what we know.

  • In laboratory research, grapefruit or orange juice at low concentrations inhibits OATP1A2 (organic anion-transporting polypeptide 1A2).
    • OATP1A2 transports selected molecules through the intestinal wall to the blood stream.
  • Grapefruit or orange juice depresses oral fexofenadine (Allegra) bioavailability (the fraction of an administered drug that reaches the systemic circulation).
  • Higher volumes of juice result in progressively lower bioavailability.
  • The reaction is due to direct inhibition of intestinal OATP1A2.
  • Naringin (a flavonoid in grapefruit that gives the juice its bitter taste) plays a major role in this interaction.
    • This suggests that other flavonoids in fruits and vegetables might produce a similar effect.
  • The duration of the juice/fexofenadine interaction is 2 to 4 hours.
    • This indicates that the interaction is avoidable if there’s an appropriate interval between drinking the juice and taking the drug.

The bottom line?

Dr. Bailey states that grapefruit juice lowers the oral bioavailability of several medications transported by OATP1A2 (eg, acebutolol [Sectral], celiprolol [Cardem], fexofenadine, talinolol [Cordanum], L-thyroxine [Synthroid]), while orange juice does the same for others (eg, atenolol [Tenormin ], celiprolol, ciprofloxacin [Cipro], fexofenadine).

Furthermore, “The interaction between grapefruit juice and etoposide [VePesid] also seemed relevant,” says the author.

The potential for an interaction doesn’t mean it’s meaningful to the patient.

In another review of drug interactions involving fruit beverages, Dr. David Greenblatt at Tufts University School of Medicine, in Boston concluded that with the exception of fexofenadine and celiprolol, “other meaningful drug interactions with fruit beverages… are not established at the present time.”

9/23/10 21:39 JR

Hi, I’m JR

John Russo, Jr., PharmD, is president of The MedCom Resource, Inc. Previously, he was senior vice president of medical communications at, a complementary and alternative medicine website.