Is it OK to combine grapefruit juice and Viagra (sildenafil)? How about Cialis or Levitra? Until it is clear what the effect is, I would say no. And because the effect of grapefruit juice lasts for 24 hours, until the effect on Viagra/Cialis/Levitra is clear, you should probably stay clear of grapefruit juice – period.

But here’s the evidence. I must admit I am a bit confused by this first study. It seems that the grapefruit juice — taken with Viagra — raises the levels of the drug. Isn’t that a good thing (assuming it doesn’t reach toxic levels)?

If I’m reading this correctly — and these pharmacokinetic studies are always tough to understand — (what exactly is area under the curve? ), it seems that this is the opposite of the pummelo study, which decreased sildenafil (Viagra) levels.

So, if I understand this, then taking Viagra with grapefruit juice should increase the levels — and possibly the effect — of Viagra in the body. I can’t advocate this, because I don’t what the effect would be, but it’s an interesting concept.

Here’s the abstract:

Clin Pharmacol Ther.
2002 Jan;71(1):21-9.
Effects of grapefruit
juice on the pharmacokinetics of sildenafil.
Jetter A1,
Kinzig-Schippers M, Walchner-Bonjean M, Hering U, Bulitta J, Schreiner P,
Sörgel F, Fuhr U.

Abstract

BACKGROUND ANDOBJECTIVES: Because of extensive first-pass metabolism, oral bioavailability of sildenafil reaches only 40%. Formation of the primary metabolite, N
-desmethylsildenafil, is mainly mediated by the cytochrome P450 enzyme CYP3A4.
In this study we investigated the influence of grapefruit juice, containing inhibitors of intestinal CYP3A4, on the pharmacokinetics of sildenafil and N-desmethylsildenafil.

METHODS: In a randomizedcrossover study, 24 healthy white male volunteers received single 50-mg doses of sildenafil. Two doses each of 250 ml grapefruit juice or water, respectively, were administered 1 hour before and together with the drug. Plasma concentrations of sildenafil and N -desmethylsildenafil were determined up to 24 hours post dose by use of liquid chromatography-tandem mass spectrometry (limit of quantification, 1 ng/ml).

RESULTS: Grapefruit juice changed the area under the sildenafil plasma concentration-time curve from time zero to infinity [AUC(0-infinity) from 620 [1.53] ng/ml x h to 761 [1.58] ng/ml x h (geometric mean with geometric standard deviation), corresponding to a 23% increase (90% confidence interval, 13%-33%). N-Desmethyl sildenafil AUC(0-infinity) increased by 24% (90% confidence interval, 17%-32%). Maximum plasma concentrations (C(max)) of sildenafil and N -desmethylsildenafil were essentially unchanged. There was a trend toward a prolonged time to reach C(max) during the grapefruit juice period (from a median of 0.75 hour to a median of 1.13 hours), corresponding to an increase by 0.25 hour (90% confidence interval, 0-0.63 hour). Interindividual variability was pronounced
in both periods.

CONCLUSIONS: Grapefruit juice increases sildenafil bioavailability and tends to delay sildenafil absorption. Sildenafil pharmacokinetics may become less predictable with grapefruit juice. Although patients usually will not be endangered by
concomitant use of grapefruit juice, it seems advisable to avoid this
combination.

However, this article says that grapefruit juice REDUCES Viagra levels, because it blocks absorption.

https://www.riverpharmacy.ca/faq/does-grapefruit-juice-affect-viagra-and-cialis-what-about-orange-or-apple-juice

A nutraceutical is a food or part of a food that allegedly provides medicinal or health benefits, including the prevention and treatment of disease. Grapefruit juice has been touted as containing many compounds that can reduce hardening of the arteries (atherosclerosis) and even the risk of cancer. Grapefruit juice can, therefore, be justifiably referred to as a classic nutraceutical. However, for many
persons taking certain medications, grapefruit juice might actually better be
termed a “nutrapollutical!”

It turns out that grapefruit juice can directly or indirectly interact in important ways with a number of medications. This is especially important since grapefruit juice is consumed by approximately one fifth of Americans for breakfast – a time of the day when medications also are commonly taken.

Grapefruit juice blocks special enzymes in the wall of the small intestine that actually destroys many medications and prevents their absorption into the body. Thus, smaller amounts of the drugs get into the body than are ingested. When the
action of this enzyme is blocked, more of the drugs get into the body and the
blood levels of these medications increase. This can lead to toxic side effects
from the medications.

Amazingly, this remarkable food-drug interaction was discovered completely by accident over a decade ago! Researchers were investigating whether alcohol could interact with felodipine (Plendil) and used a solution of alcohol with grapefruit juice to mask the taste of alcohol for the study. Researchers discovered that blood levels of felodipine were increased several fold more than in previous studies. This
increased blood level caused an increase in the effect and side effects of felodipine.
Further research revealed that the grapefruit juice itself was actually increasing the amount of the study drug in the body.

Research about the interaction of grapefruit juice with drugs suggests that compounds in grapefruit juice, called furanocoumarins (for example, bergamottin), may be responsible for the effects of grapefruit juice. Researchers believe that
furanocoumarins block the enzymes in the intestines that normally break down
many drugs. One glass of grapefruit juice could elicit the maximum blocking
effect, and the effect may persist for longer than 24 hours. Since the effects
can last for such a prolonged period of time, grapefruit juice does not have to
be taken at the same time as the medication in order for the interaction to occur.
Therefore, unlike similar interactions, where the interaction can be avoided by
separating the administration of the two interacting agents by a couple of
hours, administration of grapefruit juice with susceptible drugs should be
separated by 24 or more hours to avoid the interaction. Since this is not
practical for individuals who are taking a medication daily, they should not
consume grapefruit juice when taking medications that are affected by
grapefruit juice.