Posted by Larry Hoover on December 21, 2008, at 8:07:56
In reply to Re: Luvox(fluvoxamine) and grapefruit?, posted by Larry Hoover on December 20, 2008, at 22:55:25
Sometimes I solve problems in my sleep. This is one of those times. I'm going to answer my own question.
> Interesting how variable the results were in this sample. In at least 3 of the 10 subjects, peak blood concentration actually decreased with grapefruit juice. If you kick that one obvious outlier subject out, I bet the mean change was non-signficant (based on eye-balling the rest of the curves). I wish there were more subjects.
I noted large variability in this small sample.
> The AUC (integrated area under the curve, i.e. blood concentration times time of exposure, in nanogram hours/ml) was up 60%, rather than Cmax (maximum concentration in ng/ml), the peak blood concentration, which was up 30% (including that one outlier subject). With T1/2 (half-life) unaffected, it's hard to understand how AUC could have increased so much.
I noted increased Cmax and AUC, *without* increased half-life. That's inconsistent, if the only influence on drug concentration, and thus exposure, is metabolic breakdown. There is another influence, that I forgot about. Grapefruit influences intestinal uptake of some drugs.
The mechanism of uptake can be very complicated. There are influx pumps working at the same time as efflux pumps. Drug molecules are simultaneously pumped into the body, and out of it. It's the balance, net uptake, that determines the drug's bioavailability. Grapefruit can slow the efflux pumps, tipping the balance to higher net uptake of the drug. And just as we saw here (this is actually a good example of the phenonomenon), the effect is quite variable across a sample of different individuals. Most are not much affected, if at all, but a few are significantly influenced.
Here are a couple of links that give further details of the process.
http://www.medscape.com/viewarticle/459176_4
http://www.ncbi.nlm.nih.gov/pubmed/18855612In contrast, when a drug depends on enzyme 3A4 for metabolic destruction (or activation), grapefruit affects everyone, sometimes profoundly.
And, just for the record, drug bioavailability is affected by a number of other fruit juices, e.g. orange and apple. When a person habitually drinks these juices, and they titrate to a specific drug dose, the effect of the juice is of no consequence whatsoever. The only way its going to ever matter is if you change your fruit juice ingestion pattern significantly, *and* you happen to be one of those rarer folk who are susceptible to changes in intestinal transporter activity, *and* you're taking a drug that depends on those transporters for absorption.
The same goes for Luvox and grapefruit, btw. If your pattern has been to use both, it's of no consequence. If you're using Luvox, and you suddenly begin consuming fruit juice, you may potentially have a modest effect similar to an increase in oral dose of the drug.
Regards,
Lar
poster:Larry Hoover
thread:869370
URL: http://www.dr-bob.org/babble/20081214/msgs/870007.html