Posted by Rick on December 28, 2001, at 15:17:51
In reply to Re: RE: Using Serzone to Raise Levels of Other Meds, posted by Sunnely on December 27, 2001, at 22:52:56
I've actually entertained the idea of taking some supposedly-standardized grapefruit or grapefruit-seed supplements -- until I remembered (from one of your posts?) that grapefruit only affects drugs with substantial firt-pass metabolism. That would exclude both clonazepam and modafinil.
I've dug up some research, mostly (but not all) based on in-vitro studies, that several herbal preparations appear to be CY3A4 inhibitors. Besides grapefruit preparations, the only examples I can think of off the top of my head are Milk Thistle and Bitter Orange Peel (has some of the same constituents as grapefruit.
There have been some conflicting reports, and as you know in vitro results don't always match in vivo. St. John's Wort, for example, appeared to be a strong CYP3A4 inhibitor in vitro, but later in vivo studies suggest it is actually an inducer. And since drugs with substantial first-pass metabolism tend to be used for the studies (that includes cyclosporine, doesn't it?), I would imagine that inferring interactions with drugs like clonazepam or alprazolam would be even iffier. Maybe these (potential) CYP3A4 inhibitors tend to have their effects in the gut like grapefruit juice.
> The idea of adding a (cheaper) drug to raise the blood levels and effects of another drug had been entertained in the past. The driving force is mainly costs (Pharmacoeconomics). For example, grapefruit juice, which markedly inhibits the enzyme CYP3A4, had been entertained to be added to cyclosporine, a costly anti-rejection drug. For now, this idea had been dropped due to lack of knowledge as to risks (cyclosporine toxicity) vs. benefits (savings) of the combination. FYI, a depressed patient on Serzone (Prozac and Luvox, to some extent) and cyclosporine may unknowlingly benefit dually from the use of these antidepressants: 1) antidepressant effect and 2) lesser dose of cyclosporine used, therefore, less cost.