Posted by JGalt on November 1, 2001, at 18:48:03
In reply to Re: Modafinil+Grapefruit Juice » JGalt, posted by JohnX2 on November 1, 2001, at 12:40:30
Hunh...grapefruit juice even raises (no pun intended) blood levels of viagra. Considering the price of non-blackmarket Viagra, one would be wise to get an Rx for the highest dosage viagra (rarely much more expensive than the lower dosages), split it 4 ways, and then use grapefruit juice to make up the difference.
Anyway. Back to the modafinil and grapefruit juice for our purposes. According to "The Diagnostic and Treatment Models, FAQ 4" at http://www.bitemarks.com/dtmodels/faq4.html. "Grapefruit juice will only affect the "first-pass" small intestine - liver metabolic pathway and not any secondary elimination metabolic processes." and "Grapefruit juice did not significantly block cytochrome P-450 3A4 isozymes in the liver hepatocytes" Okay, so that answers that...if the drug in question is significantly metabolized by 1st pass elimination on the CYP 3A4 isoenzyme (also 1A2 and 3A3 to a lesser degree, however, this does help w/ keeping caffeine active, have to remember that), grapefruit juice will raise the levels which reach your blood stream. Some drugs this can have more than a 20! fold increase in blood levels (not most).
Also interesting from the same site: "The cytochrome P450 isoenzyme suppression activity of grapefruit juice was found to be accumulative, with an estimated half life at around 12 hours. The suppression effect at the enteric (gut) level, appears to be caused by a degrading (destruction) and not only suppression of the Cytochrome P450 3A4 isozyme. The return of cytochrome P450 3A4 isoenzyme activity appears to require de novo cytochrome P450 isozyme synthesis, further prolonging the effects of grapefruit juice."
K...now that that's over with...
I did a little medline research and came up with surprisingly little on enzymes and modafinil... What was shown was that chronic modafinil usage increases its own metabolism (in this case, it increased metabolism 20% after 9 weeks of daily 400mg administration) as modafinil is a mild inducer of 3A4, which is, according to the literature, is indeed a main method of metabolism. There seems to be no information on an interaction between grapefruit juice and it, but given that it is a relatively new drug and overdoses are rarely fatal, the lack of information on an interaction certainly does not mean that there isn't one.
The literature does suggest that over half of the modafinil ingested is metabolized by the liver, so it would seem that given what we know about modafinil and grapefruit juice, the interaction I had hoped for probably does not exist in amounts large enough to bother with the taste of grapefruit juice for. Of course, other drugs that use the 3A4 enzyme in the liver might represent a way of increasing levels of modafinil, but of course that drug would have to be beneficial enough to use and thus I'm probably not up for doing the research to find out if there is anything I'd like to use with modafinil that uses the 3A4 enzyme, though Rick pointed out that Klonipin does...I'm sure there are many others. Oh well, I'll just catalogue this in the back of my mind and if I have the choice of a drug that would use 3A4 in the liver and one that would not, all other things being equal, I will know I now have good reason to use the one that uses 3A4 (provided I properly reduce dosages of both). Also good to know about the grapefruit+caffeine or benzo's, viagra, and many other drugs. Thought previously it was mostly just BP meds.
JGalt
poster:JGalt
thread:82868
URL: http://www.dr-bob.org/babble/20011025/msgs/82920.html