Posted by Squiggles on July 8, 2006, at 19:15:21
In reply to Re: Rumination-snapper }} Squiggles, posted by sdb on July 8, 2006, at 18:57:54
> Here is a study but diazepam is not only metabolized by CYP3A4:
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> Eur J Drug Metab Pharmacokinet. 1998 Jan-Mar;23(1):55-9. Related Articles, Links
>
> Interaction between grapefruit juice and diazepam in humans.
>
> Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A.
>
> Department of Pharmacology, Medical Faculty, University of Osmangazi, Eskisehir, Turkey.
>
> Grapefruit juice has been reported to markedly improve the bioavailability of triazolam, midazolam, terfenadine, cyclosporine and several dihydropyridine calcium channel blockers including felodipine, nifedipine, nitrendipine and nisoldipine. Because these drugs are metabolized by the hepatic cytochrome P450 isozyme (CYP) 3A4, the inhibitory effect of grapefruit juice is thought to results from inhibition of CYP3A4. In this study, our aim was to investigate the effects of grapefruit juice on plasma concentrations of diazepam. Eight healthy male and female subjects participated in this study. Oral (5 mg) diazepam was administered with either 250 ml water and grapefruit juice. Blood samples were collected for a 24 h period, and whole blood concentrations of diazepam were measured enzyme immunoassay. The mean AUC(0-24) of diazepam was increased 3.2-fold (P < 0.001) and Cmax was increased 1.5-fold (P < 0.05) by the grapefruit juice. Grapefruit juice postponed the tmax of diazepam from 1.50 h to 2.06 h (P < 0.01).
>Interesting; drug interactions are interesting in
general but to know exactly what effect one
drug has on another, or on an enzyme or hormone
can be very useful. In this case the inhibition of grapefruit juice (not just grapefruit because
of quantity i would imagine) can be used for or
against the potentiation of these drugs. I use
the word potentiation but that may not be quite
correct. What is bioavailability? Does it mean that the blockage of cytochrome P450 isozyme represses the liver metabolism, and therefore the
stuff is voided, much like lithium's kidney voidance is increased by sodium and potassium?Also, how would you use this cytochrome blockage to the advantage of regulating the benzo dose?
It might take some fine measurement.Squiggles
poster:Squiggles
thread:662997
URL: http://www.dr-bob.org/babble/20060701/msgs/665224.html