Posted by Larry Hoover on December 20, 2008, at 22:55:25
In reply to Re: Luvox(fluvoxamine) and grapefruit? » Larry Hoover, posted by SLS on December 20, 2008, at 21:50:46
> I read that in a study of healthy volunteers, ingestion of 250 ml (approximately 8 ounces) of grapefruit juice along with fluvoxamine increased the blood level of fluvoxamine by 60%
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> http://www.cop.ufl.edu/fdic/pdfs/Gj%20-%20fluvoxamine%20interaction.pdf
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> - ScottGood find, Scott. That paper had no abstract in Pubmed.
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.
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.
My sources were e.g. Merck Manual, pharmacokinetic analyses of CYP450 products, and binding affinities at the enzyme active sites. All sources I found indicated that 3A4 was a minor pathway. I guess that would depend, however, on the relative potency of your 1A2 and 3C enzymes. There was no observed effect of poor or extensive metabolizers at 2D6, so I ignored that issue altogether. There are so many assumptions that underly what is thought of as "normal" or "typical". Nothing like a real experiment to test the assumptions.
Regards,
Lar
poster:Larry Hoover
thread:869370
URL: http://www.dr-bob.org/babble/20081214/msgs/869959.html