September #27 : Pulp Fiction...and Facts - by Lark Lands

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September 1997

Pulp Fiction...and Facts

by Lark Lands

Grapefruit juice may skew, for better or worse, the effects of some meds

Who would ever guess that your choice of breakfast beverage could influence how well your protease inhibitor works or could produce serious toxicity from your antihistamine? Yep, even a single glass of grapefruit juice can greatly increase the bloodstream level of a lengthy list of medications, potentially improving the effectiveness of some, but also creating a significant risk of increased toxicity from many.

Last May, headlines trumpeted findings from a University of Michigan study of the effects of grapefruit juice on the body's metabolism of a calcium channel blocker (felodipine, used to lower blood pressure). Unfortunately, press reports played up the potential for increasing the benefits of many drugs -- and several stories specifically mentioned protease inhibitors -- while generally failing to discuss the serious potential for creating toxic effects. Nor did the reports clarify that the effects vary widely, depending on the drug.

Most media accounts also got the science wrong -- reporting that this drink "helps the body absorb drugs." Actually, grapefruit juice lowers the intestinal breakdown of many drugs by inhibiting the intestinal enzyme (CYP3A4) involved in their metabolism. The effect on most drugs is to put a higher concentration in the bloodstream. For example, researchers at Hoffmann -- La Roche found that drinking 150 ml (around five-eighths of a cup) of reconstituted frozen grapefruit juice, both when saquinavir is taken and again an hour after the dose, leads to an average 50 percent increase in blood levels of the drug. Curiously, however, that same glass of grapefruit juice appears to decrease blood levels of Crixivan (indinavir), possibly lowering its effectiveness and increasing the chance for the development of resistance.

Moreover, anyone considering juicing up their saquinavir levels in this manner should know that every container of grapefruit juice can have a different enzyme-inhibiting effect, and that the effect may vary widely between individuals. Unfortunately, the individualized effects of using grapefruit juice can't currently be measured easily since the blood test to determine drug levels is not available outside research laboratories. Thus, if you want to try this combo you'd be winging it, unable to know precisely how effectively it might -- or might not -- be working.

Note that a lengthy list of other drugs -- in use by some PWAs -- are metabolized by CYP3A4. What follows is only a sample, based on the meager research that's been done:

  • the antihistamines terfenadine (Seldane) and astemizole (Hismanal)
  • the anticoagulant warfarin (Coumarin)
  • calcium channel blockers (drugs used in the treatment of heart disease and high blood pressure; also being used by some physicians in the treatment of neurological problems in PWAs) such as felodipine (Plendil), nifedipine (Adalat, Procardia), verapimil (Calan, Isoptin, and Verelan), and others
  • benzodiazepines (drugs including Valium, Halcion, Restoril and others used as tranquilizers or sleeping medications)
  • cyclosporine (Sandimmune, an immunosuppressive drug used with organ transplants; also being studied as a treatment for PWAs)
  • theophylline (a smooth-muscle relaxant and bronchodilator used in the treatment of asthma and of bronchial spasms associated with bronchitis or emphysema)

It's quite possible that grapefruit juice could increase the levels of many of these enough to create serious toxicity. Caveat emptor.

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