How is a glass of apple juice different from a glass of grapefruit juice?

Since the early 1990’s grapefruit juice has been well established as a precipitant of significant drug-drug interactions with nearly 200 clinical studies conducted to characterize the interactions. Recommendation to avoid grapefruit products is standard clinical practice when patients are given drugs largely metabolized by CYP3A4. Strikingly, many early studies of the effects of grapefruit juice on drug disposition were conducted using apple juice or orange juice together with water as a control.

Grapefruit juice consumption was consistently associated with increased exposures to drugs such as statins, antihypertensives and immunosuppressants while apple juice and orange juice did not seem to cause any effects. The effects of grapefruit juice were dependent on the strength and quantity of juice consumed showing a clear dose-response relationship. Things seemed very straightforward. But taking drugs with fruit juices has gotten much more complicated. Recent studies have highlighted the fact that grapefruit juice may also decrease the exposure to drugs like celiprolol, fexofenadine, aliskiren, and talinolol up to 85% via a different mechanism, inhibition of intestinal OATP uptake transporters. Most surprisingly, other fruit juices, the ones thought to be “innocent” like orange juice and apple juice or even pomelo juice, have similar effects.  Orange juice decreases the exposure to celiprolol, fexofenadine, and aliskiren to a similar magnitude as grapefruit juice.

Most interestingly, apple juice appears to decrease the exposure to drugs like fexofenadine, demonstrating that drug-drug interactions with apple juice are also a therapeutic concern. In the paper “The Pharmacokinetic Exposure to Fexofenadine is Volume-Dependently Reduced in Healthy Subjects Following Oral Administration With Apple Juice” featured in CTS, Luo and colleagues show that the greater the volume of apple juice consumed, the larger the reduction in fexofenadine exposure. This study clearly shows a dose-response effect for apple juice. After 25 years of research on the drug-drug interactions caused by fruit juices it is now clear that every fruit juice is different and very few juices are completely free of drug-drug interaction potential.

The stage is set for systematic, mechanistic studies on how fruit juices affect drug exposure. Perhaps the time has come to also take the science of fruit juice effects to clinical practice and expand label information and clinical practice beyond recommendations to avoid grapefruit juice.

Reference:

1. University of Washington Drug Interaction database accessed July 1, 2016. https://didb.druginteractioninfo.org.

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