In the February 12 2000 issue of British medical journal The Lancet, researchers with the National Institute of Health in Bethesda Maryland, reported that taking St. John’s wort, the popular herbal medication, with Crixivan (indinavir) reduces the amount of Crixivan available in the blood enough to lead to drug resistance, and therefore, possible treatment failure. St. John’s wort is thought to induce the 3A4 isoform of the cytochrome P450 (CYP) enzyme system. Crixivan, and other protease inhibitors, are metabolized by these enzymes. Induction means that St. John’s wort causes more enzyme to be produced, and therefore the drugs that are metabolized by that enzyme are processed (cleared) more quickly. The result is lower than needed amounts of the drug in the blood.

Specifically, when you swallow a Crixivan the drug gets in your blood and there is enough drug present in your body to fight HIV until you take the next dose. In this study, when the person was also taking St. John’s wort, the amount of time that Crixivan was present in sufficient amounts to fight HIV (area under the curve or AUC) was reduced by a mean of 57%. The extrapolated 8 hour Crixivan trough (minimum concentration of Crixivan in the blood) was decreased by 81%. So, if you take St. John’s wort and Crixivan together, the levels of Crixivan in your blood over an eight-hour dosing period are going to be too low to be effective against HIV. The inducing effect of St. John’s wort can last several days after you stop taking the herb because higher enzyme levels persist.