Lauren - Ten or so years ago I did study of the cytochrome-P450 system for the psychiatrists I was working with at the time. I spent weeks in the stacks at the University poring over studies, including some of the early studies involving inhibition of drug metabolism by grapefruit. This was the pre-internet days, so I really wore out my photocopy card (Hey Larry, remember the Index Medicus?).

The problem with trying to adjust (ie. lower) your medication dose and compensating by eating grapefruit is that every grapefruit will vary (at least, slightly; at most, significantly) in the amounts of enzyme inhibitors each on contains, due to differences in the size of each grapefruit and the genetic differences amongst different grapefruit trees. Granted, these differences may be small (then again they may not; I haven't seen any studies comparing enzyme inhibitor differences between different grapefruit trees), and as Larry said, you could titrate the dose, but you'd more than likely have to eat grapefruit from one tree only. That would be tough to do if you buy your grapefruit from Safeway.

The constiuents of grapefruit responsible for the inhibition of the cytochrome P-450 isoenzymes (esp. CYP1A2 and CYP3A4) are certain bioflavinoids (esp. naringen, which is converted by gut bacteria to the potent inhibitor, naringenin) and certain furanocoumarins (esp. 6,7-dihydroxybergamottin). There are several other compounds in grapefruit that inhibit CYP isoenzymes to varying degrees.

To further complicate matters, there is something in grapefruit that activates P-glycoprotein which reverses the absorption of certain drugs by actively pumping the drugs back into the intestine after they have been absorbed. This drug interaction mechanism is not thought to be clinically significant, especially when compared to the inhibition of the CYP isoenzymes by flavinoids and the furanocoumarins (et al), but the activity of P-glycoprotein pumps varies widely in individuals, due to differences in genetic make-up (ie. number of copies of the gene coding for P-glycoprotein). This could be one explanation why the extent of inhibition of drug metabolism by grapefruit is so widely variable and unpredictable in different people.

In short, I wouldn't bother trying to save on medication costs by eating grapefruit. There are just too many variables involved.

Larry (and others) - Here good website for Grapefruit-Drug Interactions . If you click on "Interactions & Clinical Significance" it lists drug categories whose metabolism is affected by grapefruit. Clicking on a category will give a detailed explanation of the significance of the interaction of individual drugs with grapefruit. To get a 2 page downloaded summary (.pdf) of drugs affected by grapefruit, and the extent to which they are affected, click on "Summary of GJDI's". I have a copy of this printed off for use at work.

I hope that all of this is of some use. - Cam