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Norvir is not the only CYP3A4 inhibitor. There are many. See the following link for an extensive discussion. Although overuse of some drugs can be toxic, even fatal, so that informed medical and pharmacological direction in dosing and using them is advisable, grapefruit juice, and especially concentrated grapefruit juice is one that is not likely to be harmful. One of the early problems noted with Saquinavir when it was introduced back in the early 90s was that it was too rapidly metabolized. published an article in Aids Treatment News on using double-strength frozen concentrated (half the water) grapefruit juice to raise SQV levels in the blood by inhibiting CYP3A4 in the liver and gut.

Abbott has alleged in its literature that the only action of Norvir at combination doses is to inhibit CYP3A4 metabolism of the combined drug. Norvir has no antiviral effect at these doses. A friendly pharmacologist may well be able to recommend a better alternative to Norvir.

Personal note: I found that it etched my front teeth at the gum line, so rinsing your mouth with water after drinking it is advisable.

Bob Emmitt

http://drnelson.utmem.edu/P450lect.html

The CYP3A subfamily is one of the most important drug metabolizing families in humans. The crystal structure of 3A4 is known, but confidential and heavily patented. CYP3A4 is "the most abundantly expressed P450 in human liver". (Arch. Biochem. Biophys. 369, 11-23 1999) The color of perfused liver is due to this protein. CYP3A4 is known to metabolize more than 120 different drugs. Some of these are well known and I give a list here of some of the recognizable ones.

CYP3A4 Substrates

There are common drugs given for special purposes that inhibit P450 enzymes. These include erythromycin (an antibiotic), ketoconazole, and itraconazole (both antifungals that inhibit the fungal CYP51 and unintentionally they also inhibit CYP3A4). If these drugs are given with other drugs that are normally metabolized by P450 enzymes, the lifetime of these other drugs will be prolonged, and plasma levels will be increased, since they won't be cleared as fast. If these drugs affect heart rhythms or other critical systems, the result can be fatal. For example, inhibition of CYP3A4 in a patient taking warfarin can cause bleeding.

Another example is ketoconazole. Studies in 1993 (Honig) showed a 15-72 fold increase in terfenadine AUC (Area under the curve) due to inhibition of CYP3A4 by ketoconazole. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia. TDP is a side-effect that has led to withdrawal of several drugs from the market including terfenadine. This is a case where a 72 fold increase in drug dose might harm or even kill a patient.

Another factor in drug dosage is interfering substances from food. Grapefruit juice contains a CYP3A4 inhibitor that causes about a 12 fold increase in some drug concentrations. And the effect lasts for several days. It is advisable to discourage your patients from drinking grapefruit juice while on medication metabolized by CYP3A4.